DILATRANE 300 mg Gél LP Plq/30

VIDAL
Medicines
Update of 01/07/2023

DILATRANE^® prolonged-release capsule at 50 mg and at 300 mg
theophylline

Forms and presentations

Prolonged-release capsule at 50 mg or at 300 mg:  Boxes of 30, under blister packs.

Composition

	p capsule
Theophylline	50 mg
or	300 mg

Excipients (common): neutral microgranules (corn starch, sucrose), ethylcellulose, methacrylic acid-methyl methacrylate copolymer (Eudragit L), povidone, talc. Capsule shell: gelatin (capsules at 50 mg and at 300 mg), indigotine (capsule at 50 mg).

Indications

• Asthma with paroxysmal dyspnea.
  
• Asthma with continuous dyspnea.
  
• Spastic forms of chronic obstructive bronchopneumopathies.
  

Theophylline is not the first-line treatment for asthma.

Dosage and administration

Dosage

• The dosage at 300 mg does not allow the delivery of a dosage suitable for a child weighing less than 40 kg (approximately 13 years).
  

The dosage will be adapted to individual susceptibility according to the therapeutic effect and adverse effects.

Treatment will be started with a moderate initial dose in order to test individual tolerance; this will then be adjusted gradually by increasing or decreasing the dose in steps until a therapeutic effect without adverse effects is obtained.

Plasma levels reach a steady state after at least 3 consecutive days of well-conducted treatment; this minimum period must be respected to judge the therapeutic effect before each dose increase.

In case of therapeutic insufficiency and in the absence of signs of intolerance, the dose will be gradually increased under monitoring of theophyllinemia, in steps of 2 mg/kg/day.

In children older than 30 months, below a daily dose of 16 mg/kg/day (adjusted to ideal weight in case of obesity) and not exceeding, in all cases, 400 mg/day, and in the absence of risk factors for reduced plasma clearance, monitoring of theophyllinemia is nevertheless not essential to the safety of use of the product.

Effective plasma theophylline concentrations usually lie between 5 and 12 µg/ml, but concentrations up to a maximum of 20 µg/ml may be necessary. The toxicity threshold of theophyllinemia is 20 µg/ml.

For reference:

Method of administration:

Oral use.

The capsule will be swallowed with a glass of water.

The capsule must not be opened.

Contraindications

Intolerance to theophylline.
Child under 30 months.

Warnings and precautions

Warnings:
Precautions for use
Use with caution in cases of:

• heart failure (reduce doses if necessary),
  
• hepatic insufficiency,
  
• obesity (adjust the dosage relative to ideal weight),
  
• coronary insufficiency,
  
• hyperthyroidism,
  
• history of seizures,
  
• gastroduodenal ulcer: in animals, experimental data have shown that theophylline has a stimulating effect on gastric secretion; its administration must be cautious in subjects with an active gastroduodenal ulcer,
  
• of prolonged fever of more than 24 hours, above 38 °C, particularly in young children (halve the dosage due to the risk of overdose, through decreased clearance of theophylline).
  

Interactions

Capsules at 50 mg:

Capsules at 300 mg:

• Do not use the combination with troleandomycin, which may cause a risk of overdose. Caution is advised with erythromycin, which may increase blood concentrations of theophylline. This risk remains to be evaluated for other macrolides.
  
• Cimetidine increases the blood concentration of theophylline: in case of concomitant administration, reduce the dose of theophylline.
  

Fertility, pregnancy and breastfeeding

Pregnancy:

In case of administration at the end of pregnancy, possibility of tachycardia and hyperexcitability in the newborn.

Adverse effects

The reported adverse effects are listed below by System Organ Class (SOC) and by frequency. Frequencies cannot be estimated from the available data (frequency unknown).

SOC (MedDRA)	Frequency	Adverse reaction
Psychiatric disorders	Frequency not known	Irritability Agitation Nervousness Excitation Insomnia
Nervous system disorders	Frequency not known	Headache Tremors Convulsions
Cardiac disorders	Frequency not known	Tachycardia Palpitations
Gastrointestinal disorders	Frequency not known	Nausea Vomiting Epigastric pain

These adverse effects may be the first signs of an overdose. The onset of convulsions is a sign of confirmed intoxication, but it may be the first sign, particularly in children.

Paediatric population:

In children with gastro-oesophageal reflux, administration of theophylline may worsen the reflux.

Rarely, possibility of digestive ulcerations with haemorrhage and obstructive syndrome.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres. Website: https://signalement.social-sante.gouv.fr.

Overdose

Paediatric population:

Agitation, irritability, nervousness, logorrhoea, tremors, mental confusion, repeated vomiting, hyperthermia, tachycardia, ventricular fibrillation, palpitations, convulsions, hypotension, hypokalaemia, hyperglycaemia, metabolic acidosis, respiratory disorders, hyperventilation then respiratory depression.

In adults:

Signs of overdose vary from one individual to another; the following are mainly observed:

• nausea, vomiting, epigastric pain;
  
• tachycardia, hypotension;
  
• irritability, nervousness, tremors, headaches, insomnia, excitation, disorientation, delirium;
  
• hypokalaemia, hyperglycaemia, metabolic acidosis;
  
• convulsions, hyperthermia and cardiac arrest.
  

Action to be taken:

• Gastric lavage, intensive care in a specialised setting, activated charcoal by oral route.
  
• Theophylline is dialysable.
  

Pharmacokinetics

The metabolism of theophylline is essentially hepatic (90% of the absorbed dose); elimination is then mainly renal, 10% to 13% are excreted in unchanged form.

Storage conditions

Store at a temperature below 25 °C.

HANDLING/DISPOSAL INSTRUCTIONS

No special requirements.

Prescription, supply and reimbursement

LIST II

Marketing authorisation (AMM)	3400932787821 (1986, SmPC rev 17.07.2019) 50 mg.
	3400932787999 (1986, SmPC rev 17.07.2019) 300 mg.

Not reimbursable and not approved for community use.

SERP
Le Triton, 5, rue du Gabian. MC 98000 Monaco
Tel: 00 377 97 77 87 05. Fax: 00 377 92 16 78 27