Lufyllin-GG Solution

LUFYLLIN®-GG is not indicated in the management of status asthmaticus, which is a serious medical emergency.

Although the relationship between plasma levels of dyphylline and appearance of toxicity is unknown, excessive doses may be expected to be associated with an increased risk of adverse effects.

General: Use LUFYLLIN®-GG with caution in patients with severe cardiac disease, hypertension, hyperthyroidism, acute myocardial injury or peptic ulcer.

Drug interactions: Synergism between xanthine bronchodilators (e.g., theophylline), ephedrine and other sympathomimetic bronchodilators has been reported. This should be considered whenever these agents are prescribed concomitantly.

Concurrent administration of dyphylline and probenecid, which competes for tubular secretion, has been shown to increase plasma half-life of dyphylline (see Clinical Pharmacology).

Carcinogenesis, mutagenesis, impairment of fertility: No long-term animal studies have been performed with LUFYLLIN®-GG.

Pregnancy: Teratogenic effects Pregnancy Category C. Animal reproduction studies have not been conducted with LUFYLLIN®-GG. It is also not known whether the product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. LUFYLLIN®-GG should be given to a pregnant woman only if clearly needed.

Nursing mothers: Dyphylline is present in human milk at approximately twice the maternal plasma concentration. Caution should be exercised when LUFYLLIN®-GG is administered to a nursing woman.

Pediatric use: Safety and effectiveness in children below the age of six have not been established. Use caution when administering to children six years of age or older.

To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LUFYLLIN®-GG may cause nausea, headache, cardiac palpitation and CNS stimulation. Postprandial administration may help avoid gastric discomfort.

The following adverse reactions which have been reported with other xanthine bronchodilators, and which have most often been related to excessive drug plasma levels, should be considered as potential adverse effects when dyphylline is administered:

Gastrointestinal: nausea, vomiting, epigastric pain, hematemesis, diarrhea.

Central nervous system: headache, irritability, restlessness, insomnia, hyperexcitability, agitation, muscle twitching, generalized clonic and tonic convulsions.

Cardiovascular: palpitation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, ventricular arrhythmias.

Respiratory: tachypnea.

Renal: albuminuria, gross and microscopic hematuria, diuresis.

Other: hyperglycemia, inappropriate ADH syndrome.

There have been no reports, in the literature, of overdosage with LUFYLLIN®-GG. However, the following information based on reports of theophylline overdosage are considered typical of the xanthine class of drugs and should be kept in mind.

Signs & symptoms: Restlessness, anorexia, nausea, vomiting, diarrhea, insomnia, irritability, and headache. Marked overdosage with resulting severe toxicity has produced agitation, severe vomiting, dehydration, excessive thirst, tinnitus, cardiac arrhythmias, hyperthermia, diaphoresis, and generalized clonic and tonic convulsions. Cardiovascular collapse has also occurred, with some fatalities. Seizures have occurred in some cases associated with very high theophylline plasma concentrations, without any premonitory symptoms of toxicity.

Treatment: There is no specific antidote for overdosage with drugs of the xanthine class. Symptomatic treatment and general supportive measures should be instituted with careful monitoring and maintenance of vital signs, fluids and electrolytes. The stomach should be emptied by inducing emesis if the patient is conscious and responsive, or by gastric lavage, taking care to protect against aspiration, especially in stuporous or comatose patients. Maintenance of an adequate airway is essential in case oxygen or assisted respiration is needed. Sympathomimetic agents should be avoided but sedatives such as short-acting barbiturates may be useful.

Dyphylline is dialyzable and, although not recommended as a routine procedure in overdosage cases, hemodialysis may be of some benefit when severe intoxication is present or when the patient has not responded to general supportive and symptomatic treatment.

Dosage should be individually titrated according to the severity of the condition and the response of the patient.

Usual adult dosage:
30 mL (two tablespoonfuls) oral solution, four times daily.

Children above age six:
15 to 30 mL (one to two tablespoonfuls) oral solution, three or four times daily.

Not recommended for use in children below age six: (see Precautions).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling nervous and excitable.
• Restlessness.
• Upset stomach or throwing up.
• Headache.
• Loose stools (diarrhea).
• Belly pain.
• Not able to sleep.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.