Alomide
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Alomide - Scientific Information

Manufacture: Alcon
Country: Canada
Condition: Conjunctivitis, Keratitis, Keratoconjunctivitis
Class: Ophthalmic antihistamines and decongestants
Form: Liquid solution, Eye drops (ophthalmic)
Ingredients: lodoxamide, benzalkonium chloride 0.007% w/v as preservative, as well as mannitol, hydroxypropyl methylcellulose, sodium citrate, tyloxapol,citric acid, edetate disodium, purified water

Pharmaceutical information

Drug Substance

Proper Name: lodoxamide tromethamine
Chemical Name: N, N'-(2-chloro-5-cyano-m-phenylene) dioxamic acid tromethamine salt.
Structural Formula:
Molecular Formula: C19H28ClN5O12
Molecular Weight: 553.91
Physical Form: White to off white powder or crystals

Composition

ALOMIDE is a sterile isotonic solution containing lodoxamide 0.1% w/v (as 0.178% w/v lodoxamide tromethamine), benzalkonium chloride 0.007% w/v as preservative, as well as mannitol, hydroxypropyl methylcellulose, sodium citrate, tyloxapol,citric acid, edetate disodium, and purified water.

Dosage form

Availability

ALOMIDE is supplied in natural plastic ophthalmic DROPTAINER* dispensers containing 10 mL or in natural plastic unit dose containers each containing 0.4 mL.

Storage

Store at room temperature (15°C – 25°C).

Information to patient

Indications

Your doctor has prescribed ALOMIDE solution for you to treat the symptoms of allergy (itching, discomfort, tearing etc) in your eyes. Regular use of this product is essential to obtain relief from your allergic symptoms.

Precautions

  1. Remove your contact lenses before using ALOMIDE solution.
  2. Wait at least 15 minutes after using ALOMIDE solution before inserting your lenses.
  3. Do not touch the dropper tip to any surface to avoid contamination.

Instructions

Put one drop into each eye, four times per day at regular intervals (about every 4 hours) while awake. It is necessary to use ALOMIDE solution regularly to obtain relief from your allergic eyes.

Pharmacology

Pharmacodynamics

Lodoxamide, a mast cell stabilizer, inhibits the in vivo type I immediate hypersensitivity reaction in animals and man. Allergen-induced bronchospasms and reduced pulmonary function in monkeys are prevented with lodoxamide treatment. A cutaneous vascular permeability increase associated with reagin or IgE and antigen mediated reactions in rats, monkeys and humans are inhibited with lodoxamide therapy. A similar vascular reaction in the palpebral conjunctiva of rats has been inhibited with topical ocular administration of lodoxamide. Therefore, it is anticipated that lodoxamide will be useful in the treatment of ocular diseases where type I immediate hypersensitivity plays a major role in the pathogenesis.

In vitro studies have demonstrated the ability of lodoxamide to stabilize mast cells and prevent the antigen specific induced release of histamine. In addition, lodoxamide prevents the release of other mast cell inflammatory mediators (i.e. SRS-A, slow reacting substances of anaphylaxis, also known as the peptido-leukotrienes) and appears to inhibit eosinophil chemotaxis. Lodoxamide inhibits histamine release in vitro by preventing the movement of calcium into the mast cell after stimulation.

In a multi-centre double-masked study (9 centres), 0.1% lodoxamide was more effective than 2% sodium cromoglycate in the treatment of the signs and symptoms of conjunctivitides of an allergic nature (vernal, giant papillary, atopic/allergic types). ocular signs and symptoms were generally controlled in fourteen to twenty-one days of therapy (q.i.d. dosing), and improvement continued with further therapy. Based upon physician and patient judgements, a therapeutic effect was observed within seven days of the initiation of treatment. In a similar single centre study, 0.1% lodoxamide was judged more effective than 2% sodium cromoglycate, but the difference was not statistically significant.

Lodoxamide has no intrinsic vasoconstrictor, antihistaminic, cyclooxygenase inhibition or other anti-inflammatory activity.

Pharmacokinetics:

The disposition of 14C-lodoxamide was studied in six healthy adult volunteers receiving a 3 mg (50 μCi) oral dose of lodoxamide. Urinary excretion was the major route of elimination. The elimination half-life of 14C-lodoxamide was 8.5 hours in urine. In a study conducted in twelve healthy adult volunteers, topical administration of ALOMIDE, one drop in each eye four times per day for ten days, did not result in any measurable lodoxamide plasma levels at a detection limit of 2.5 ng/ml.

Toxicology

Acute Toxicity

Species/Route LD50 (mg/kg) Signs of Toxicity
Mouse, i.p closed eyes. 4,000 - 5,000 Depression, laboured breathing, partially
Mouse, i .p 3634 Depression, prostration, coma.
Mouse, p.o >5,000 None
Rat, p.o >4,000 None
Rat, p.o. >5,000 None
Rat, i.p 5.019 Altered gait, thirstiness, prostration, coma.
Rat, i.p. >5,000 Slight amount of blood tinged abdominal fluid.

Chronic Toxicity

Species/Route Daily Dosage (mg/kg) Signs of Toxicity
Mouse, p.o
14 days
0, 500, 1600, 5,000 None
Dog, p.o.
One month
10, 30, 100 None
Mouse, p.o
3 months
0, 500, 1600, 5,000 None
Rat, p.o
1, 3 months
10, 30, 100 Decreases in erythrocyte
parameters in females
Rat, p.o
1 year
10, 30, 100 Dose related decrease in body
weights in males. Small renal
calculi (relationship questionable).
Monkey, p.
l year
10, 30, 100 No overt effects
Rat, p.
2 yea
(carcinogenicity)
10, 30, 100 Comparable to controls.

Mutagenicity

Test System Result
Ames (Salmonella) (3 strains)
with and without activation
Negative up to
2,000 ug/plate
Ames (Salmonella) (2 additional strains)
with and without metabolic activation
Negative
250-2,000 ug/plate

Reproduction and Teratology

Species/Route Dosage (mg/kg/day) Findings
Rat, p.o Segment l 30 - Male
10, 30 - Female
No adverse effects.
Rat, p.o Segment l 10, 30, 100 Possible decrease in proportion of
litter surviving.
Rat, p.o Segment 2 10, 30 No adverse effects.
Rat, p.o Segment 2 10, 30, 100 Not teratogenic.
Rat, p.o Segment 3 10, 30 No adverse effects.
Rat, p.o Segment 3 10, 30, 100 No adverse effects.
Rabbit, p.o Segment 2 10, 30, 100 No adverse effects.
Rabbit, p.o Segment 2 10, 30 No adverse effects.

Ocular Studies

Species Dosage (mg/kg) Signs of Toxicity
Rabbit
Ocular Irritation
14 days
0.1%, 1%
both eyes BID
Reddening of eyelids-
comparable to control
Rabbit
Ocular Irritation
Every 30 mins.
for 12 doses
(1 day)
0.25%
0.5%
1%
right eye
В В В 
Minimal-moderate
conjunctival congestion
and discharge; minimal
fluorescein staining.
Comparable to controls.
Rabbit
Ocular Irritation
1, 3 months
with HPMC-0.25%
0.5, l%
w.o HPMC-0.5%
right eye; QID
Minimal-moderate conjunctival
congestion and discharge.
Sporadic and transient instances of
superficial corneal epithelium,
irregularities (not dose related) in product
and vehicle with HPMC.
Monkey
Ocular Irritation
3 months
0.25, 0.5, 1%None
right eye; QID