Theophyllin symptoms and conditions

If anyone has any access to databases that can describe the history of drug licensing in other countries and whether Merck had to amend product statements, this is worth investigating. I do know that montelukast was at least not initially licensed for seasonal allergies in the United Kingdom when the FDA granted approval in the US. As of 2006, seasonal allergies were not on the approved listed in the UK.

More to add to the files:

Safety of leukotriene antagonists
United Kingdom — The Medicines Control Agency
has published a review of adverse drug reactions to
a new class of asthma drugs, leukotriene antagonists.
Zafirlukast and moltelukast, competitive cysteinyl
leukotriene type-1 receptor antagonists, were
both marketed for the first time in 1998.
Cysteinyl leukotrienes are inflammatory mediators
and potent constrictors of bronchial smooth muscle
that attract human eosinophils and cause airway
oedema, mucus hypersecretion and reduced
mucociliary clearance. By blocking this action, leukotriene
antagonists can improve respiratory function
and lessen symptoms in patients with asthma.
The pharmacological action of leukotrienes is quite
complex and varying side effects have been
reported. Zafirlukast inhibits the hepatic cytochrome
P4502C9, and interacts with warfarin, theophyllin,
terfenadine, acetylsalicylic acid and erythromycin.
Montelukast is metabolized by hepatic cytochrome
P450CYP3A4 and co-administration of such drugs
as phenytoin, phenobarbitone and rifampicin, which
induce this enzyme, result in a marked reduction in
plasma levels.
Side-effects identified during clinical trials were
headache, abdominal pain, nausea, diarrhoea,
gastro-enteritis, influenza, pharyngitis, sinusitis,
cough, nasal congestion, dizziness, fatigue and insomnia.
Since marketing of montelukast, 173 reports
of 317 suspected adverse drug reactions
have been received in the United Kingdom. These
include oedema (50), psychiatric reactions, including
including agitation/restlessness (15), allergy, including
anaphylaxis, angioedema and urticaria (10), chest
pain (7), tremor (5), mouth dryness (5), vertigo (4)
and arthralgia (3).
Reference: Current Problems in Pharmacovigilance,
Volume 24, August 1998.
https://www.who.ch/druginformation/vol12/12-4.pdf