Restophylline

Restophylline Uses, Dosage, Side Effects, Food Interaction and all others data.

Restophylline is a combination of theophylline and ethylenediamine. Ethylenediamine is inactive; it increases the solubility of theophylline in water. Theophylline relaxes bronchial smooth muscle. Suggested mechanisms are an increase in intracellular cAMP through inhibition of phosphodiesterase; adenosine receptor antagonism, prostaglandin antagonism and effects on intracellular calcium.

Restophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion.

Trade Name Restophylline
Availability Discontinued
Generic Aminophylline
Aminophylline Other Names Aminofilina, Aminophyllin, Aminophylline, Aminophyllinum
Related Drugs albuterol, dexamethasone, methylprednisolone, theophylline, Ventolin, Xopenex, Ventolin HFA, caffeine, Theo-Dur, Theo-24
Weight 100mg
Type Tablet
Formula C16H24N10O4
Weight Average: 420.4264
Monoisotopic: 420.198199306
Protein binding

60%

Groups Approved
Therapeutic Class Methyl xanthine derivatives, Respiratory stimulants: analeptics, Theophylline & related drugs
Manufacturer Gaco Pharmaceuticals Ltd
Available Country Bangladesh
Last Updated: September 19, 2023 at 7:00 am
Restophylline
Restophylline

Uses

It is used for the treatment and prophylaxis of bronchospasm associated with asthma, emphysema and chronic bronchitis. Also used for adults for the treatment of cardiac asthma and left ventricular or congestive cardiac failure.

Restophylline is also used to associated treatment for these conditions: Acute Exacerbation of Chronic Bronchitis (AECB), Asthma, Bronchial Asthma, Bronchospasm, Chronic Bronchitis, Exacerbation of asthma

How Restophylline works

Restophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Dosage

Restophylline dosage

Oral:Chronic bronchospasm:

  • Adult: As hydrate: Initially, 225-450 mg bid, increased if necessary.
  • Child: >3 yr: As modified-release hydrate: 12 mg/kg daily increased to 24 mg/kg daily in 2 divided doses after 1 wk.

Intravenous:Acute severe bronchospasm:

  • Adult: Loading dose: 5 mg/kg (ideal body weight) or 250-500 mg (25 mg/ml) by slow inj or infusion over 20-30 min. Maintenance infusion dose: 0.5 mg/kg/hr. Max rate: 25 mg/min.
  • Child: Loading dose: same as adult dose. Maintenance dose: 6 mth-9 yr: 1 mg/kg/hr and 10-16 yr: 0.8 mg/kg/hr.
  • Elderly: Dose reduction may be necessary.
  • Hepatic impairment: Dose reduction may be necessary.

Tablets should be swallowed whole and not chewed because of the structure of the tablet.

Side Effects

The most common adverse effects are gastric irritation, nausea, vomiting, diarrhea, hematemesis, epigastric pain and tremor. These are usually early signs of toxicity; however, with high doses, ventricular arrhythmias or seizures may be the first signs to appear and reactivation of peptic ulcer, headache, irritability, restlessness, insomnia, twitching, convulsion and reflex hyperexcitability, palpitation, tachycardia, hypotension, circulatory failure, ventricular arrhythmias, and flushing, albuminuria, diuresis and hematuria. Also inappropriate ADH syndrome may occur.

Precaution

Restophylline should be given with caution to patients with peptic ulceration, hyperthyroidism, hypertension, cardiac arrhythmias or other cardiovascular disease, or epilepsy, as these conditions may be exacerbated. They should also be given withcaution to patients with heart failure, hepatic dysfunction, chronic alcoholism, acute febrile illness, and to neonates and the elderly, since in all of these circumstances theophylline clearance may be decreased, resulting in increases in serum-theophylline concentrations and serum half-life.

Food Interaction

  • Administer vitamin supplements. Restophylline may reduce Vitamin B6 levels as an adverse effect. Consider supplementation.
  • Avoid excessive or chronic alcohol consumption. Ingesting a large amount of alcohol may reduce aminophylline clearance, therefore increasing its serum concentration.
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of aminophylline.
  • Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of aminophylline. Therefore it may reduce the serum concentration and effectiveness of aminophylline.
  • Limit caffeine intake. Excessive caffeine intake with aminophylline may exacerbate caffiene-like side effects such as nausea, nervousness, irritability, insomnia and tremors.
  • Take with food. This may reduce gastric irritation. Restophylline absorption is slower when taken with food.

Restophylline Hypertension interaction

[Moderate] The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations.

Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs.

Therapy with theophyllines should be administered cautiously in such patients.

Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects.

Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

Volume of Distribution

  • 0.3 to 0.7 L/kg

Half Life

7-9 hours

Clearance

  • 0.29 mL/kg/min [postnatal age 3-15 days]
  • 0.64 mL/kg/min [postnatal age 25-57 days]
  • 1.7 mL/kg/min [ 1-4 years]
  • 1.6 mL/kg/min [4-12 years]
  • 0.9 mL/kg/min [13-15 years]
  • 1.4 mL/kg/min [16-17 years]
  • 0.65 mL/kg/min [Adults (16-60 years), non-smoking asthmatics]
  • 0.41 mL/kg/min [Elderly (>60 years). liver, and renal function]
  • 0.33 mL/kg/min [Acute pulmonary edema]
  • 0.54 mL/kg/min [COPD->60 years, stable non-smoker >1 year]
  • 0.48 mL/kg/min [COPD with cor pulmonale]
  • 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
  • 0.31 mL/kg/min [Liver disease -cholestasis]
  • 0.35 mL/kg/min [cirrhosis]
  • 0.65 mL/kg/min [acute hepatitis]
  • 0.47 mL/kg/min [Sepsis with multi-organ failure]
  • 0.38 mL/kg/min [hypothyroid]
  • 0.8 mL/kg/min [hyperthyroid]

Pregnancy & Breastfeeding use

Use of aminophylline in pregnant women should be balanced against the risk of uncontrolled disease.

Contraindication

Restophylline should not be administered to patients with hypersensitivity to xanthines or ehylenediamine. It should not be administered to patients with active peptic ulcer, since it may increase the volume and acidity of gastric secretions.

Innovators Monograph

You find simplified version here Restophylline

Restophylline contains Aminophylline see full prescribing information from innovator Restophylline Monograph, Restophylline MSDS, Restophylline FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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