Doxofylline is a methylxanthine derivative with the presence of a dioxolane group in position 7. As a drug used in the treatment of asthma, doxofylline has shown similar efficacy to theophylline but with significantly fewer side effects in animal and human studies. Unlike other xanthines, doxofylline lacks any significant affinity for adenosine A1 or A2 receptors and does not produce stimulant effects. Decreased affinity for adenosine receptors may account for the better safety profile of doxofylline compared to theophylline. Unlike theophylline, doxofylline does not affect calcium influx and does not antagonize the actions of calcium channel blockers which could explain reduced cardiac adverse reactions associated with the drug . The anti-asthmatic effects of doxophylline are mediated by other mechanisms, primarily through inhibiting the activities of the phosphodiesterase (PDE) enzyme.
Unlike other xanthines, doxofylline lacks any significant affinity for adenosine A1 or A2 receptors and does not produce stimulant effects. Decreased affinity for adenosine receptors may account for the better safety profile of doxofylline compared to theophylline Unlike theophylline, doxofylline does not affect calcium influx and does not antagonize the actions of calcium channel blockers which could explain reduced cardiac adverse reactions associated with the drug.
Mechanism of action of doxofylline
The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation.
The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking . Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed . Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation.
There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study . It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro .Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells
Indications of doxofylline
- Shortness of breath
- Asthma attack
- COPD (Chronic Obstructive Pulmonary Disease) and bronchial asthma.
- Chronic asthmatic bronchitis.
- Indicated for the treatment of chronic obstructive pulmonary disease (COPD), bronchial asthma and pulmonary disease with spastic bronchial component.
It has antitussive and bronchodilator effects, and acts as a phosphodiesterase inhibitor.
Contraindications of doxofylline
Dosages of doxofylline
- 400 mg (1 tablet) daily in the evening. However, in certain cases, 400 mg twice daily is recommended on the basis of the clinical response. Doses as high as 1200 mg/day (400 mg 3 times daily) may also be prescribed. In elderly patients with concomitant cardiovascular, hepatic and renal diseases recommended dosage should be 200 mg twice daily.
Children (above 6 years of age)
- The recommended dosage of Doxofylline is 6 mg/kg twice daily. The dose may be increased up to 18 mg/kg daily on the basis of clinical response.
Dosage Type: 6 mg/kg b.i.d
- Weight of the Child: 10 kg > Dosage: 3 ml
- Weight of the Child: 15 kg > Dosage: 4.5 ml
- Weight of the Child: 20 kg > Dosage: 6 ml
- Weight of the Child: 25 kg > Dosage: 7.5 ml
- Weight of the Child: 30 kg > Dosage: 9 ml
- Weight of the Child: 35 kg > Dosage: 10.5 ml
- Weight of the Child: 40 kg > Dosage: 12 ml
Dosage Type: Total Daily Dose
- Weight of the Child: 10 kg > Dosage: 6 ml
- Weight of the Child: 15 kg > Dosage: 9 ml
- Weight of the Child: 20 kg > Dosage: 12 ml
- Weight of the Child: 25 kg > Dosage: 15 ml
- Weight of the Child: 30 kg > Dosage: 18 ml
- Weight of the Child: 35 kg > Dosage: 21 ml
- Weight of the Child: 40 kg > Dosage: 24 ml
Doxofylline may be taken with or without food.
Side Effects of doxofylline
The most common
- sore throat
- unable to sleep
- stomach pain
- dizziness, drowsiness
- upper respiratory tract infection.
- runny nose
- headache, dizziness, drowsiness
- stomach pain
- nausea, vomiting
- agitation, including aggressive behaviour and/or hostility
- irritability, restlessness, feeling anxious
- seeing, feeling or hearing things that are not there (also called hallucinations)
- dream abnormalities, difficulty sleeping
- sleep walking.
- muscle aches or cramps, joint pain
- stomach pain
- nausea, vomiting
- Abdominal or stomach pain
- general feeling of discomfort or illness
- joint pain
- pain or tenderness around the eyes and cheekbones
- shortness of breath or troubled breathing
- tightness of the chest
Drug Interactions of doxofylline
Doxofylline may interact with following drugs,suppliment & may change the efficasy of drugs
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine,risperidone)
- antiseizure medications (e.g., clobazam, phenobarbital, phenytoin, valproic acid, )
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- Calcium channel blockers, diltiazem, verapamil
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- magnesium sulfate
- monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, rasagiline, selegiline,tranylcypromine)
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine, citalopram)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, )
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- “triptan” migraine medications (e.g., eletriptan, sumatriptan)
- tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
FDA Pregnancy Category B
When phenytoin is taken during pregnancy, it may cause harm to the developing baby. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
This medication passes into breast milk. If you are a breast-feeding mother and are taking phenytoin, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding