URAMOX

PIL- clean 09.2020

Patient leaflet in accordance with the Pharmacists' Regulations (Preparations) - 1986

This medicine is dispensed with a doctor’s prescription only

URAMOX

®

, Tablets

Name and quantity of active ingredient: Each tablet contains:

250 mg acetazolamide

For a list of inactive ingredients and allergens please see section 2 under ‘Important information

about some of this medicine’s ingredients’ and section 6 ‘Additional information’.

Read the entire leaflet carefully before you start using this medicine. This leaflet contains

concise information about this medicine. If you have any further questions, consult your doctor

or pharmacist.

This medicine has been prescribed to treat your illness. Do not pass it on to others. It may harm

them, even if it seems to you that their illness is similar to yours.

1. What is this medicine intended for?

As a supplementary treatment of edema that is due to heart failure or is caused by

medication.

As a supplementary treatment of different types of glaucoma.

To relieve and prevent acute mountain sickness.

Therapeutic group: carbonic anhydrase inhibitor.

2. Before using this medicine

Do not use this medicine if:

you are sensitive (allergic) to sulphonamides, sulphonamide derivatives including

acetazolamide or to any of the other ingredients in this medicine (please see section 6).

you have severe liver problems.

you have or have ever had severe kidney problems.

you have a particular type of glaucoma known as chronic non-congestive angle-closure

glaucoma (your doctor will be able to advise you).

you have reduced function of the adrenal glands - glands above the kidneys (also known as

Addison’s disease).

you have low blood levels of sodium and/or potassium or high blood levels of chlorine (your

doctor will advise you).

you are pregnant.

Special warnings about using this medicine

Before starting treatment with Uramox, tell your doctor if:

you have lung problems, such as chronic bronchitis or emphysema, which cause

difficulty in breathing.

you have, or have ever had, kidney problems, such as kidney stones.

you are over the age of 65.

This medicine may affect certain medical tests. If you undergo any medical tests, tell the

doctor that you are taking Uramox.

Other medicines and Uramox

PIL- clean 09.2020

If you are taking or have recently taken other medicines, including nonprescription

medications and dietary supplements, tell your doctor or pharmacist. Particularly if you are

taking:

medicines for the heart, such as cardiac glycosides (such as digoxin)

medicines to reduce blood pressure

medicines to thin the blood (such as warfarin)

medicines to lower sugar in the blood (such as: metformin, gliclazide)

medicines for epilepsy or convulsions (mainly phenytoin, primidone, carbamazepine or

topiramate)

medicines that affect the metabolism of folic acid, such as: methotrexate,

pyrimethamine, or trimethoprim

steroids such as prednisolone

aspirin and similar medicines, such as salicylic acid or choline salicylate for mouth ulcers

other medicines in the group of medicines called carbonic anhydrase inhibitors (such as

dorzolamide or brinzolamide which are also used to treat glaucoma)

amphetamines (stimulants), quinidine (treats an irregular heartbeat), methenamine

(prevents urinary tract infections) or lithium (treats severe mental problems)

sodium bicarbonate therapy (used to treat high levels of acid in the body)

ciclosporin (used to suppress the immune system)

Using this medicine and food

Swallow the medicine with water. Take this medicine with or immediately after a meal.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby,

consult your doctor or pharmacist before taking any medicines.

Pregnancy

Do not take the medicine if you are pregnant, think you are pregnant or are planning to have a

baby.

Breastfeeding

If you are breastfeeding, you may take this medicine only after consulting your doctor.

Driving and using machines

If the medicine makes you feel drowsy or confused, do not drive or operate machines. The

medicine may occasionally cause short-sightedness. If this happens and you feel that you can

no longer drive safely, you should stop driving and contact your doctor.

Important information about some of this medicine’s ingredients

The medicine contains lactose. If you have been told by your doctor that you have an

intolerance to certain sugars, consult a doctor before taking the medicine.

This medicine contains less than 1 millimole sodium (23 mg) per tablet, so it is essentially

‘sodium free’.

3. How to use this medicine?

Always use this medicine according to your doctor's instructions. Check with your doctor or

pharmacist if you are not sure about your dose or about how to take this medicine.

The dosage varies from person to person, depending on their condition.

PIL- clean 09.2020

Only your doctor will determine your dose and how you should take this medicine. The

recommended dosage is usually:

Glaucoma:

Adults: 250-1,000 mg (1-4 tablets) a day, in divided doses.

Edema:

Adults: Starting dose is 250-375 mg (1-1.5 tablets) once a day in the morning. Your doctor will

adjust the dose and tell you how often to take your dose.

Mountain sickness:

2-4 tablets a day, in divided doses.

In case of rapid ascent (such as in rescue operations), the recommended dosage is 4 tablets a

day.

It is preferable to begin treatment 24-48 hours before ascent and continue for 48 hours while at

high altitudes or for as long as necessary to relieve symptoms.

Do not chew! The tablet can be split in half or crushed if necessary.

Do not exceed the recommended dose.

If you have accidentally taken a higher dose, or if a child has accidentally swallowed some

medicine, immediately see a doctor or go to a hospital emergency room and bring the medicine

package with you.

If you forget to take this medicine at the scheduled time, take a dose as soon as you

remember. However, if the next dose is due in two hours or less, skip the forgotten dose and

continue taking the tablets at their regular times. Never take two doses together to make up for

a forgotten dose.

Adhere to the treatment as recommended by your doctor.

Even if your health improves, do not stop taking this medicine without consulting your doctor.

Do not take medicines in the dark! Check the label and the dose each time you take

medicine. Wear glasses if you need them.

If you have any further questions about using this medicine, consult your doctor or

pharmacist.

4. Side effects

Like with all medicines, using Uramox may cause side effects in some users. Do not be alarmed

by this list of side effects; you may not experience any of them.

Consult a doctor immediately:

All medicines can cause allergic reactions, although serious allergic reactions are very

rare. If you experience sudden wheezing, difficulty in breathing, swelling of the eyelids,

face or lips, rash or itching (especially affecting the whole body), consult a doctor

immediately.

Uramox may affect the cells in your blood so you may be at a higher risk of infections

and your blood may not clot properly. If you have a sore throat or fever or you notice

bruises or tiny red or purple spots on your skin, consult your doctor immediately. If your

muscles feel weak or you have spasms, consult a doctor immediately.

PIL- clean 09.2020

Uramox may affect the liver and kidneys. If you experience pain in the lower back, pain

or burning when passing urine, have difficulty in passing urine or you stop passing urine,

have blood in your urine, pale stools, or if your skin or eyes look slightly yellow, consult a

doctor. In addition, contact a doctor if your stools are black or tarry, or if you notice blood

in your stools.

Rare cases of skin rashes, including increased sensitivity to sunlight, have been

reported. If you develop any unusual skin rashes, consult a doctor.

Additional side effects

Side effects whose frequency is unknown (frequency has not been established yet):

headache, diarrhea, nausea or vomiting, loss of appetite, thirst, metallic taste in the mouth,

dizziness, loss of full control of hands or legs, flushing, increased frequency of passing urine,

tiredness or irritability, feeling overexcited, a feeling of numbness or tingling in the fingers or

toes, or coldness in the extremities; depression, drowsiness or confusion, decreased interest in

sex, ringing in the ears or difficulty in hearing, temporary short-sightedness which subsides

when the dosage is reduced or treatment is stopped.

Rare cases of skin rashes including an increased sensitivity to sunlight have been reported. If

you experience any unusual skin rashes, inform your doctor.

When taking Uramox for a long time, the medicine can affect the level of potassium or sodium in

your blood. Your doctor may perform blood tests to make sure that this is not happening.

With long-term therapy you might also experience bone thinning or be at risk of kidney stones.

High or low blood sugar levels may occasionally occur.

Consult a doctor immediately if you experience a serious skin reaction: a red, scaly rash with

bumps under the skin and blisters (exanthematous pustulosis). The frequency of this side

effects is not known (cannot be estimated from the available data).

If you experience any side effect, if any side effect gets worse, or if you experience a side

effect not mentioned in this leaflet, consult your doctor.

You can report side effects to the Ministry of Health by following the link ‘Reporting Side

Effects of Drug Treatment' on the Ministry of Health home page www.health.gov.il which links

to an online form for reporting side effects. You can also use this link:

https://sideeffects.health.gov.il

5. How to store the medicine?

Prevent poisoning! To prevent poisoning keep this, and all other medicines, in a closed

place, out of the reach and sight of children and/or infants. Do not induce vomiting unless

explicitly instructed to do so by a doctor.

Do not use the medicine after the expiry date (exp. date) that appears on the package. The

expiry date refers to the last day of that month.

Storage conditions

Store below 25°C.

Do not discard medicines in the wastewater or waste bin. Ask the pharmacist how to discard

medicines you no longer use. These measures will help protect the environment.

Shelf-life after opening the medicine: 8 months.

PIL- clean 09.2020

6. Additional information

In addition to the active ingredient, this medicine also contains:

lactose monohydrate, corn starch, talc, gelatin, glycerin, sodium starch glycolate, magnesium

stearate.

What the medicine looks like and contents of the pack:

white, round tablets, with “T53” written on one side and a score line on the other side.

Bottle of 30 tablets with a child-proof cap.

Manufacturer and license holder: Taro Pharmaceutical Industries Ltd., 14 Hakitor Street,

Haifa Bay 2624761.

Registration number of the medicine in the Ministry of Health’s National Drug Registry:

016 94 21225 00

Revised in May 2020.

Uramox SPC – final 05.20

Uramox

®

1. Name of the medicinal product

URAMOX

Acetazolamide 250mg Tablets

2. Qualitative and quantitative composition

Each tablet contains 250mg acetazolamide.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Tablet.

White, round tablet one side engraved with "T53". Other side cross scored.

4. Clinical particulars

4.1.

Therapeutic indications

Uramox tablets are for oral administration.

Uramox is an enzyme inhibitor which acts specifically on carbonic anhydrase.

It is indicated for:

1. Adjunctive treatment of drug induced edema and edema due to congestive

heart failure.

2. Chronic simple (open angle) glaucoma, secondary glaucoma and pre

operatively in acute angle closure glaucoma where delay of surgery is

desired in order to lower intraocular pressure.

3. Acute mountain sickness.

4.2.

Posology and method of administration

Congestive Heart Failure

: For diuresis in congestive heart failure, the

starting dose is usually 250 to 375 mg once daily in the morning. If, after an

initial response, the patient fails to continue to lose edema fluid, do not

increase the dose but allow for kidney recovery by skipping medication for a

day. Acetazolamide tablets yield best diuretic results when given on

alternate days, or for two days alternating with a day of rest.

Failures in therapy may be due to overdosage or too frequent dosage. The

use of acetazolamide does not eliminate the need for other therapy such as

digitalis, bed rest and salt restriction.

Drug Induced Edema:

Recommended dosage is 250 to 375 mg of

acetazolamide once a day for one or two days, alternating with a day of rest.

Glaucoma:

Acetazolamide should be used as an adjunct to the usual

therapy. The dosage employed in the treatment of chronic simple (open-

angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours,

usually in divided doses for amounts over 250 mg. It has usually been found

Uramox SPC – final 05.20

that a dosage in excess of 1 g per 24 hours does not produce an increased

effect. In all cases the dosage should be adjusted with careful individual

attention both to symptomatology and ocular tension. Continuous

supervision by a physician is advisable.

In treatment of secondary glaucoma and in the postoperative treatment of

some cases of acute congestive (close-angle) glaucoma, the preferred

dosage is 250 mg every four hours, although some cases have responded

to 250 mg twice daily on short-term therapy. In some acute cases, it may be

more satisfactory to administer an initial dose of 500 mg followed by 125 or

250 mg every four hours depending on the individual case.

A complementary effect has been noted when acetazolamide has been

used in conjunction with miotics or mydriatics as the case demanded.

Acute Mountain Sickness:

Dosage is 500 mg to 1,000 mg daily, in divided

doses. In circumstances of rapid ascent such as in rescue or military

operations, the higher dose level of 1,000 mg is recommended. It is

preferable to initiate dosing 24 to 48 hours before ascent and to continue for

48 hours while at high altitude, or longer as necessary to control symptoms.

The change from other medication to Uramox should be gradual.

Elderly: Uramox should only be used with particular caution in elderly

patients or those with potential

obstruction in the urinary tract or with

disorders rendering their electrolyte balance precarious or with liver

dysfunction.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed

in section 6.1.

Acetazolamide is contra-indicated in situations in which sodium and/or

potassium blood levels are depressed, in

cases of marked kidney and liver

disease or dysfunction, suprarenal gland failure, and hyperchloremic

acidosis.

Uramox should not be used in patients with hepatic cirrhosis as

this may increase the risk of hepatic

encephalopathy.

Long-term administration of Uramox is contra-indicated in patients with

chronic non-congestive angle-closure

glaucoma since it may permit

organic closure of the angle to occur while the worsening glaucoma is

masked by

lowered intraocular pressure.

Uramox should not be used in patients hypersensitive to sulphonamides.

4.4.

Special warnings and precautions for use

Increasing the dose does not increase the diuresis and may

increase the incidence of drowsiness and/or

paraesthesia.

Increasing the dose often results in a decrease in diuresis. Under certain

circumstances, however, very large doses

have been given in

Uramox SPC – final 05.20

conjunction with other diuretics in order to secure diuresis in complete

refractory failure.

When Uramox is prescribed for long-term therapy, special precautions

are advisable. The patient should be

cautioned to report any unusual

skin rash. Periodic blood cell counts and electrolyte levels are

recommended.

Fatalities have occurred, although rarely, due to severe

reactions to sulphonamides. A precipitous drop in formed

blood cell

elements or the appearance of toxic skin manifestations should call for

immediate cessation of Uramox

therapy.

In patients with pulmonary obstruction or emphysema where alveolar

ventilation may be impaired, Uramox may

aggravate acidosis and

should be used with caution.

In patients with a past history of renal calculi, benefit should be

balanced against the risks of precipitating further

calculi.

The occurrence at the treatment initiation of a feverish generalized

erythema associated with pustule may be a symptom of acute

generalized exanthematous pustulosis (AGEP) (See section 4.8). In

case of AGEP diagnosis, acetazolamide should be discontinued and

any subsequent administration of acetazolamide contraindicated.

4.5.

Interaction with other medicinal products and other forms of

interaction

Uramox is a sulphonamide derivative. Sulphonamides may potentiate the

effects of folic acid antagonists. Possible

potentiation of the effects of folic

acid antagonists, hypoglycaemics and oral anti-coagulants may occur.

Concurrent

administration of acetazolamide and aspirin may result in

severe acidosis and increase central nervous system

toxicity. Adjustment

of dose may be required when Uramox is given with cardiac glycosides or

hypertensive agents.

When given concomitantly, acetazolamide modifies the metabolism of

phenytoin, leading to increased serum levels of

phenytoin. Severe

osteomalacia has been noted in a few patients taking acetazolamide in

combination with other

anticonvulsants. There have been isolated reports

of reduced primidone and increased carbamazepine serum levels

with

concurrent administration of acetazolamide.

Because of possible additive effects, concomitant use with other

carbonic anhydrase inhibitors is not advisable.

By increasing the pH of renal tubular urine, acetazolamide reduces the

urinary excretion of amphetamine and quinidine and so may enhance

the magnitude and the duration of effect of amphetamines and

enhance the effect of quinidine.

Ciclosporin: acetazolamide may elevate ciclosporin levels.

Methenamine: acetazolamide may prevent the urinary antiseptic effect of

Uramox SPC – final 05.20

methenamine.

Lithium: acetazolamide increases lithium excretion and the blood lithium levels

may be decreased.

Sodium bicarbonate: acetazolamide and sodium bicarbonate used

concurrently increases the risk of renal calculus

formation.

4.6.

Pregnancy and lactation

Pregnancy

Acetazolamide has been reported to be teratogenic and embryotoxic in

rats, mice, hamsters and

rabbits at oral or parenteral doses in excess of

ten times those recommended in human beings. Although there is no

evidence of these effects in human beings, there are no adequate and

well-controlled studies in pregnant women.

Therefore, Uramox should not

be used in pregnancy, especially during the first trimester.

Breast-feeding

Uramox has been detected in low levels in the milk of lactating women who

have taken Uramox.

Although it is unlikely that this will lead to any harmful

effects in the infant, extreme caution should be exercised when

Uramox is

administered to lactating women.

Fertility

Not available

4.7.

Effects on ability to drive and use machines

Increasing the dose does not increase the diuresis and may increase the

incidence of drowsiness and/or

paraesthesia. Less commonly, fatigue,

dizziness and ataxia have been reported. Disorientation has been

observed in

a few patients with oedema due to hepatic cirrhosis. Such

cases should be under close supervision. Transient myopia

has been

reported.

These conditions invariably subside upon diminution or discontinuance of the

medication.

4.8.

Undesirable effects

The following adverse reactions are classified by system organ class

and ranked under heading of frequency using the following convention:

Not known: frequency cannot be estimated from the available data

System organ

class

Frequency

Adverse reactions

Blood and lymphatic

Not known

Thrombocytopenia,

Uramox SPC – final 05.20

system

disorders

leukopenia, aplastic

anaemia, bone marrow

depression,

pancytopenia,

agranulocytosis****

Metabolism and nutrition

disorder

Not known

Metabolic acidosis,

electrolyte imbalance*

thirst**

Psychiatric disorders

Not known

Depression, irritability,

reduced libido, occasional

instances of

confusion

Nervous system

disorders

Not known

Paraesthesia, particularly

a “tingling” feeling in the

extremities, dizziness,

headache, occasional

instances of drowsiness,

convulsions, flaccid

paralysis

Eye disorders

Not known

Transient myopia***

Ear and labyrinth

disorders

Not known

Impaired hearing

and tinnitus

Gastrointestinal

disorders

Not known

Melaena, taste

disturbance, nausea,

vomiting, diarrhoea

Hepatobiliary

disorders

Not known

Fulminant hepatic

necrosis****, hepatitis or

cholestatic jaundice

Skin and subcutaneous

tissue

disorders

Not known

Urticaria, rash (including

Erythema multiforme,

Stevens-Johnson

syndrome, Toxic

epidermal necrolysis)****,

thrombocytic purpura,

photosensitivity, acute

generalized

exanthematous pustulosis

(AGEP)

Renal and urinary

disorders

Not known

Haematuria,

crystalluria****, renal and

ureteral colic****, renal

lesions, renal failure,

calculus

formation****,

glycosuria, polyuria

General disorders and

administration site

conditions

Not known

Fever****, fatigue,

anaphylaxis****,

flushing

Uramox SPC – final 05.20

Investigations

Not known

Abnormal liver

function

* During long-term therapy, metabolic acidosis and electrolyte imbalance

may occasionally occur. This can usually be

corrected by the

administration of bicarbonate.

**Adverse reactions during short-term therapy are usually non-serious.

***This condition invariably subsides upon diminution or withdrawal of the

medication.

****Uramox is a sulphonamide derivative and therefore some side-

effects similar to those caused by sulphonamides

have occasionally

been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal

product is important. It allows continued monitoring of the benefit/risk

balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health

according to the National Regulation by using an online form:

https://sideeffects.health.gov.il

4.9.

Overdose

No specific antidote. Supportive measures with correction of electrolyte and

fluid balance. Force fluids.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Carbonic anhydrase inhibitors.

ATC Code: S01EC01

Acetazolamide is an inhibitor of carbonic anhydrase. By inhibiting the

reaction catalysed by this enzyme in the renal

tubules, acetazolamide

increases the excretion of bicarbonate and of cations, chiefly sodium and

potassium, and so

promotes alkaline diuresis.

Continuous administration of acetazolamide is associated with metabolic

acidosis and resultant loss of diuretic

activity. Therefore, the effectiveness

of Uramox in diuresis diminishes with continuous use.

By inhibiting carbonic anhydrase in the eye, acetazolamide decreases

intra-ocular pressure and is therefore useful in

the treatment of glaucoma.

5.2 Pharmacokinetic properties

Absorption

Uramox SPC – final 05.20

Acetazolamide is fairly rapidly absorbed from the gastro-intestinal tract with

peak plasma concentrations occurring

about 2 hours after administration

by mouth.

Distribution

It has been estimated to have a plasma half-life of about 4 hours. It is

tightly bound to carbonic anhydrase and accumulates in tissues containing

this enzyme, particularly red blood cells

and the renal cortex. It is also

bound to plasma proteins.

Elimination

It is excreted unchanged in the urine; renal clearance being

enhanced in

alkaline urine.

5.3 Preclinical safety data

Not applicable

6. Pharmaceutical particulars

6.1 List of excipients

Lactose monohydrate, corn starch, talc, gelatin, glycerin, magnesium

stearate, sodium starch glycolate

6.2 Incompatibilities

None.

6.3 Shelf life

The expiry date of the product is indicated on the packaging materials.

Shelf life after opening: 8 months.

6.4 Special precautions for storage

Store below 25°C

6.5 Nature and contents of container

HDPE plastic bottle, with a child-proof PP cap.

Each package contains 30 tablets.

6.6 Special precautions for disposal and other handling

None.

7.

Marketing authorisation holder

Taro Pharmaceutical Industries Ltd.,

Uramox SPC – final 05.20

14 Hakitor St., Haifa Bay 2624761

8.

Marketing authorisation number(s)

01694.21225

Revised in May 2020.