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What is Theophylline and Aminophylline
Theophylline is a xanthine derivative that is used both orally or intravenously in the treatment of asthma and bronchospasm; aminophylline is a pro-drug of theophylline and is also used intravenously and orally.
Aminophylline is converted to theophylline; 1 mg aminophylline is equivalent to 0.8 mg theophylline. The drugs have a narrow therapeutic range and theophylline toxicity is well documented.
Theophylline occurs naturally in tea and is chemically similar to caffeine and theobromine.
Theophylline was introduced in 1900 to treat asthma, but its use did not become widespread until after 1936, and it was not approved by the FDA until 1940.
During the 1970s and 1980s, theophylline dosing was intensively studied, its pharmacokinetics were accurately described, and sustained-release preparations were marketed.
There is contradictory evidence regarding the effectiveness of low-dose theophylline on exacerbation rates in chronic obstructive pulmonary disease (COPD); in general, the drug has a moderate bronchodilator effect that may result in additive but mild improvements in FEV-1 when added to beta-agonists.
However, the risk for toxicity increases at dosages that produce therapeutic benefit.
According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, theophylline and aminophylline are not recommended for the treatment of COPD and should not be used in acute COPD exacerbations due to the low efficacy at recommended doses and the potential for adverse reactions and toxicity.
Use of theophylline is also not routinely recommended for asthma maintenance therapy.
The FDA no longer includes acute bronchospasm due to status asthmaticus as an approved indication for parenteral products.
The Expert Panel of the National Asthma Education and Prevention Program (NAEPP) does not recommend theophylline or aminophylline for acute asthma exacerbations because it appears to provide no additional benefit to optimal inhaled beta-2-agonist therapy and may increase risk of adverse effects.
Sustained-release oral theophylline is considered an alternate, but not preferred, therapy to the use of inhaled corticosteroids (ICSs) in the treatment of mild persistent asthma (step 2 care) according to the Expert Panel of the NAEPP.
In addition, the Panel recommends theophylline as an alternate, adjunct therapy with low-dose ICS for patients with inadequately controlled moderate persistent asthma (step 3 care).
An alternate treatment in step 4 care includes the combined use of theophylline and ICS.
Modest clinical effectiveness as well as the need for monitoring theophylline levels should be taken into consideration when evaluating the benefits and risks of chronic theophylline treatment compared to other asthma and COPD treatments.
Indications
- asthma
- bradycardia
- bronchospasm prophylaxis
- chronic bronchitis
- chronic obstructive pulmonary disease (COPD)
- emphysema
- neonatal apnea
- sleep apnea
- status asthmaticus
Side Effects
- abdominal pain
- agitation
- anaphylactoid reactions
- anorexia
- anxiety
- atrial fibrillation
- atrial flutter
- atrial tachycardia
- cardiac arrest
- contact dermatitis
- diarrhea
- diuresis
- dizziness
- exfoliative dermatitis
- gastroesophageal reflux
- headache
- hematemesis
- hyperactivity
- hypercalcemia
- hyperglycemia
- hypokalemia
- hypotension
- insomnia
- irritability
- metabolic acidosis
- nausea
- palpitations
- premature ventricular contractions (PVCs)
- pruritus
- rash
- restlessness
- rhabdomyolysis
- seizures
- sinus tachycardia
- supraventricular tachycardia (SVT)
- tremor
- urticaria
- ventricular tachycardia
- vitamin B6 deficiency
- vomiting
Monitoring Parameters
- blood pressure
- heart rate
- LFTs
- pulmonary function tests (PFTs)
- serum theophylline concentrations
Contraindications
- acidemia
- breast-feeding
- cardiac arrhythmias
- cardiac disease
- cholestasis
- cor pulmonale
- corn hypersensitivity
- coronary artery disease
- cystic fibrosis
- fever
- gastritis
- gastroesophageal reflux disease (GERD)
- geriatric
- heart failure
- hepatic disease
- hepatitis
- hiatal hernia
- hyperthyroidism
- hypothyroidism
- hypoxemia
- infants
- myocardial infarction
- neonates
- peptic ulcer disease
- pregnancy
- prostatic hypertrophy
- pulmonary edema
- renal impairment
- seizure disorder
- sepsis
- shock
- tobacco smoking
Interactions
- Acetaminophen; Aspirin, ASA; Caffeine
- Acetaminophen; Butalbital
- Acetaminophen; Butalbital; Caffeine
- Acetaminophen; Butalbital; Caffeine; Codeine
- Acetaminophen; Caffeine
- Acetaminophen; Caffeine; Dihydrocodeine
- Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
- Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
- Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
- Acetaminophen; Dextromethorphan; Phenylephrine
- Acetaminophen; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Dichloralphenazone; Isometheptene
- Acetaminophen; Guaifenesin; Phenylephrine
- Acetaminophen; Pseudoephedrine
- Aclidinium; Formoterol
- Acrivastine; Pseudoephedrine
- Acyclovir
- Adenosine
- Albendazole
- Albuterol
- Albuterol; Ipratropium
- Allopurinol
- Alpha interferons
- Alprazolam
- Amifampridine
- Amiodarone
- Amitriptyline; Chlordiazepoxide
- Amobarbital
- Amoxicillin; Clarithromycin; Lansoprazole
- Amoxicillin; Clarithromycin; Omeprazole
- Amphetamine
- Amphetamine; Dextroamphetamine
- Amphetamine; Dextroamphetamine Salts
- Anagrelide
- Antithyroid agents
- Aprepitant, Fosaprepitant
- Arformoterol
- Armodafinil
- Articaine; Epinephrine
- Aspirin, ASA; Butalbital; Caffeine
- Aspirin, ASA; Butalbital; Caffeine; Codeine
- Aspirin, ASA; Caffeine; Dihydrocodeine
- Aspirin, ASA; Caffeine; Orphenadrine
- Aspirin, ASA; Dipyridamole
- Atazanavir
- Atazanavir; Cobicistat
- Atropine; Hyoscyamine; Phenobarbital; Scopolamine
- Azelastine
- Azelastine; Fluticasone
- Barbiturates
- Belladonna Alkaloids; Ergotamine; Phenobarbital
- Benzodiazepines
- Benzphetamine
- Beta-agonists
- Blinatumomab
- Boceprevir
- Brodalumab
- Brompheniramine; Carbetapentane; Phenylephrine
- Brompheniramine; Hydrocodone; Pseudoephedrine
- Brompheniramine; Pseudoephedrine
- Budesonide; Formoterol
- Bupropion
- Bupropion; Naltrexone
- Butabarbital
- Caffeine
- Caffeine; Ergotamine
- Canakinumab
- Cannabidiol
- Capmatinib
- Carbamazepine
- Carbetapentane; Chlorpheniramine; Phenylephrine
- Carbetapentane; Diphenhydramine; Phenylephrine
- Carbetapentane; Guaifenesin; Phenylephrine
- Carbetapentane; Phenylephrine
- Carbetapentane; Phenylephrine; Pyrilamine
- Carbetapentane; Pseudoephedrine
- Carbinoxamine; Dextromethorphan; Pseudoephedrine
- Carbinoxamine; Hydrocodone; Phenylephrine
- Carbinoxamine; Hydrocodone; Pseudoephedrine
- Carbinoxamine; Phenylephrine
- Carbinoxamine; Pseudoephedrine
- Ceritinib
- Cetirizine
- Cetirizine; Pseudoephedrine
- Charcoal
- Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
- Chlophedianol; Guaifenesin; Phenylephrine
- Chlordiazepoxide
- Chlordiazepoxide; Clidinium
- Chlorpheniramine; Dextromethorphan; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
- Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Hydrocodone; Phenylephrine
- Chlorpheniramine; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Phenylephrine
- Chlorpheniramine; Pseudoephedrine
- Cimetidine
- Ciprofloxacin
- Clarithromycin
- Clonazepam
- Clorazepate
- Cobicistat
- Codeine; Phenylephrine; Promethazine
- Colesevelam
- Darunavir
- Darunavir; Cobicistat
- Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
- Desloratadine; Pseudoephedrine
- Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
- Dexmethylphenidate
- Dextroamphetamine
- Dextromethorphan; Diphenhydramine; Phenylephrine
- Dextromethorphan; Guaifenesin; Phenylephrine
- Dextromethorphan; Guaifenesin; Pseudoephedrine
- Diazepam
- Dichlorphenamide
- Diethylpropion
- Dihydrocodeine; Guaifenesin; Pseudoephedrine
- Diltiazem
- Diphenhydramine; Hydrocodone; Phenylephrine
- Diphenhydramine; Phenylephrine
- Dipyridamole
- Disulfiram
- Dobutamine
- Dopamine
- Dronabinol
- Dronedarone
- Drospirenone; Ethinyl Estradiol
- Drospirenone; Ethinyl Estradiol; Levomefolate
- Duloxetine
- Dupilumab
- Dyphylline
- Dyphylline; Guaifenesin
- Echinacea
- Elbasvir; Grazoprevir
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
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- Emapalumab
- Enflurane
- Ephedrine
- Epinephrine
- Erythromycin
- Erythromycin; Sulfisoxazole
- Estazolam
- Ethinyl Estradiol
- Ethinyl Estradiol; Desogestrel
- Ethinyl Estradiol; Ethynodiol Diacetate
- Ethinyl Estradiol; Etonogestrel
- Ethinyl Estradiol; Levonorgestrel
- Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
- Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
- Ethinyl Estradiol; Norelgestromin
- Ethinyl Estradiol; Norethindrone
- Ethinyl Estradiol; Norethindrone Acetate
- Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
- Ethinyl Estradiol; Norethindrone; Ferrous fumarate
- Ethinyl Estradiol; Norgestimate
- Ethinyl Estradiol; Norgestrel
- Ethotoin
- Etomidate
- Famotidine
- Famotidine; Ibuprofen
- Febuxostat
- Fexofenadine; Pseudoephedrine
- Fluconazole
- Flurazepam
- Fluticasone; Salmeterol
- Fluticasone; Umeclidinium; Vilanterol
- Fluticasone; Vilanterol
- Fluvoxamine
- Formoterol
- Formoterol; Mometasone
- Fosphenytoin
- Givosiran
- Glycerol Phenylbutyrate
- Glycopyrrolate; Formoterol
- Golimumab
- Green Tea
- Guaifenesin; Hydrocodone; Pseudoephedrine
- Guaifenesin; Phenylephrine
- Guaifenesin; Pseudoephedrine
- Halothane
- Hydantoins
- Hydrochlorothiazide, HCTZ; Propranolol
- Hydrocodone; Phenylephrine
- Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
- Hydrocodone; Pseudoephedrine
- Hydroxyprogesterone
- Ibuprofen; Pseudoephedrine
- Idelalisib
- Imipenem; Cilastatin
- Imipenem; Cilastatin; Relebactam
- Indacaterol
- Indacaterol; Glycopyrrolate
- Infliximab
- Interferon Alfa-2a
- Interferon Alfa-2b
- Interferon Alfa-2b; Ribavirin
- Interferon Alfa-n3
- Interferon Alfacon-1
- Interferon Gamma-1b
- Iopamidol
- Isavuconazonium
- Isoflurane
- Isoniazid, INH
- Isoniazid, INH; Pyrazinamide, PZA; Rifampin
- Isoniazid, INH; Rifampin
- Isoproterenol
- Ixekizumab
- Ketamine
- Ketoconazole
- Lansoprazole
- Lansoprazole; Naproxen
- Leflunomide
- Lesinurad; Allopurinol
- Letermovir
- Levalbuterol
- Levocetirizine
- Levothyroxine
- Levothyroxine; Liothyronine (Porcine)
- Levothyroxine; Liothyronine (Synthetic)
- Liothyronine
- Lisdexamfetamine
- Lithium
- Lopinavir; Ritonavir
- Loratadine; Pseudoephedrine
- Lorazepam
- Lumacaftor; Ivacaftor
- Mephobarbital
- Mepivacaine; Levonordefrin
- Mestranol; Norethindrone
- Metaproterenol
- Methacholine
- Methamphetamine
- Methohexital
- Methotrexate
- Methylphenidate
- Metreleptin
- Mexiletine
- Midazolam
- Midodrine
- Mitotane
- Modafinil
- Moricizine
- Mycophenolate
- Nabilone
- Naproxen; Pseudoephedrine
- Neuromuscular blockers
- Nilutamide
- Norepinephrine
- Obeticholic Acid
- Olodaterol
- Ombitasvir; Paritaprevir; Ritonavir
- Oritavancin
- Osilodrostat
- Oxazepam
- Paroxetine
- Pazopanib
- Peginterferon Alfa-2a
- Peginterferon Alfa-2b
- Pemoline
- Pentobarbital
- Pentoxifylline
- Phendimetrazine
- Phenobarbital
- Phentermine
- Phentermine; Topiramate
- Phenylephrine
- Phenylephrine; Promethazine
- Phenytoin
- Pirbuterol
- Posaconazole
- Prednisone
- Prilocaine; Epinephrine
- Primidone
- Propafenone
- Propofol
- Propranolol
- Pseudoephedrine
- Quazepam
- Quinine
- Rabeprazole
- Racepinephrine
- Regadenoson
- Rifampin
- Rifapentine
- Riociguat
- Ritodrine
- Ritonavir
- Rofecoxib
- Roflumilast
- Ropivacaine
- Rucaparib
- Salmeterol
- Sarilumab
- Secobarbital
- Secukinumab
- Segesterone Acetate; Ethinyl Estradiol
- Semaglutide
- Sevelamer
- Sevoflurane
- Siltuximab
- Simeprevir
- Sincalide
- St. John’s Wort, Hypericum perforatum
- Sucralfate
- Sulfinpyrazone
- Sympathomimetics
- Tacrine
- Tacrolimus
- Teduglutide
- Telaprevir
- Telithromycin
- Telotristat Ethyl
- Temazepam
- Terbinafine
- Terbutaline
- Teriflunomide
- Thiabendazole
- Thiopental
- Thyroid hormones
- Ticlopidine
- Tiotropium; Olodaterol
- tobacco
- Tocilizumab
- Trandolapril; Verapamil
- Triazolam
- Umeclidinium; Vilanterol
- Vemurafenib
- Verapamil
- Zafirlukast
- Zileuton