(S)-3-[3-(tert-Butylamino)-2-hydroxypropoxy]-4-morpholino-1,2,5-thiadiazolmonomaleat

This chemical does not meet GHS hazard criteria for 1.1% (1 of 89) of reports.

Danger

H302 (98.9%): Harmful if swallowed [Warning Acute toxicity, oral]；H361 (92.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H372 (39.3%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P203, P260, P264, P270, P280, P301+P317, P318, P319, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 89 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 89 reports by companies.；There are 9 notifications provided by 88 of 89 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

IMAP assessments - 2-Propanol, 1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-, (S)-, (Z)-2-butenedioate (1:1) (salt): Environment tier I assessment；IMAP assessments - 2-Propanol, 1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-, (S)-, (Z)-2-butenedioate (1:1) (salt): Human health tier I assessment

Drug Induced Liver Injury Rank (DILIrank 2.0)

Timolol maleate

Ambiguous-DILI-concern

5

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation；Because of the variability in excretion of timolol into breastmilk and minimal reported experience during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.；Ophthalmic use of timolol by the mother should pose little risk to the breastfed infant, although some guidelines state that gel formulations are preferred over solutions. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. The manufacturer of Combigan states that it is not recommended for use during lactation, but there is no evidence for this statement.；◉ Effects in Breastfed Infants；None reported, but beta-adrenergic blocking drugs with similar breastmilk excretion characteristics have caused adverse effects in breastfed newborns.；No side effects were reported in one case report of a 9-week-old breastfed infant whose mother was using 0.5% ophthalmic timolol drops twice daily in one eye.；A mother who was taking 2 drops of timolol 0.5% eye drops daily as well as using pilocarpine eye drops twice daily and acetazolamide 250 mg orally twice daily and delivered a preterm infant at 36 weeks of gestation. The infant began 5 months of exclusive breastfeeding at 6 hours after birth. On day 2, the infant developed electrolyte abnormalities consisting of hypocalcemia, hypomagnesemia, and metabolic acidosis. The infant was treated with oral calcium gluconate and a single dose of intramuscular magnesium sulfate. Despite continued breastfeeding and maternal drug therapy, the infant's mild metabolic acidosis disappeared on day 4 of life and the infant was gaining weight normally at 1, 3 and 8 months, but had mild hypotonicity. The authors considered the metabolic effects to be caused by transplacental passage of acetazolamide that resolved despite the infant being breastfed. The infant gained weight adequately during breastfeeding, but had some mild, residual hypertonicity of the lower limbs requiring physical therapy.；A newborn infant was breastfed during maternal therapy with various combinations of ocular timolol, dipivifrin, dorzolamide, brimonidine and several doses of acetazolamide. Ultimately, the mother was treated with timolol gel-forming solution 0.5% and dorzolamide 2% drops. The drugs were given immediately following breastfeeding with punctal occlusion and no apnea or bradycardia was observed in the infant.；◉ Effects on Lactation and Breastmilk；Relevant published information on the effects of beta-blockade or timolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol.

TIMOLOL MALEATE

Adrenergic beta-Antagonists [MoA]; beta-Adrenergic Blocker [EPC]

TIMOLOL MALEATE OPHTHALMIC

beta-Adrenergic Blocker [EPC]; Adrenergic beta-Antagonists [MoA]

TIMOLOL MALEATE OPHTHALMIC GEL FORMING

beta-Adrenergic Blocker [EPC]; Adrenergic beta-Antagonists [MoA]

Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.