Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Undesirable effects can occur with the following frequencies: Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000, including isolated reports), not known (cannot be estimated from the available data).
The following effects have been reported and are listed below by body system: 
MedDRA                               Frequency                  Undesirable effects system organ class database
Blood and lymphatic system disorders                  Uncommon              Thrombocytopenia 
Rare               Eosinophilia
Leukopenia
Bone marrow depression
(necessitates withdrawal of treatment). The haemopoietic status should therefore be regularly monitored.

Very Rare             Aplastic anemia or hemolytic anemia
Agranulocytosis
Nervous system disorders                                 Rare               Paresthesia 

Hyperosmolar coma
Not known   Dizziness, syncope and loss of consciousness    (caused    by symptomatic hypotension).

Eye disorders                                        Uncommon    Visual disturbance 
Ear and labyrinth disorders                          Uncommon    Deafness (sometimes irreversible)

Rare      Hearing disorders and tinnitus1

Cardiac arrhythmias                                  Uncommon    Cardiac arrhythmias 
Hepatobiliary disorders                              Not known   Cholestasis Intrahepatic (In isolated cases)
Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see
Section 4.3).

Vascular Disorder                        Uncommon                Hypotension2 
Rare                    Vasculitis

Not Known               Thrombosis8
Skin and subcutaneous tissue disorders   Uncommon                Photosensitivity 
Rare                    Skin and mucous membrane reactions may occasionally occur, e.g., Itching, urticaria,
other rashes or bullous lesions,
fever, hypersensitivity to light,
exudative erythema multiforme
(Lyell's syndrome and Stevens-
Johnson syndrome), bullous exanthema, exfoliative dermatitis, purpura, AGEP (acute generalized exanthematous pustulosis) and DRESS (Drug rash with eosinophilia and systemic symptoms)

Not Known               Bullous Pemphigoid
Metabolism and nutrition disorders       Not Known               Symptomatic electrolyte disturbances and Metabolic alkalosis3
Metabolic acidosis4
Hyponatremia5
Hypokalemia6
Reduction of serum HDL- cholesterol, elevation of serum
LDL-cholesterol and elevation of serum triglycerides. During long term therapy they will usually return to normal within six months
Hypocalcemia and
Hypomagnesemia7
Hypovolemia and dehydration8


Psychiatric disorders                          Rare                             Mental disorder 
Congenital, familial and genetic disorders     Not Known                        Patent ductus arteriosus9 
General disorders and administration site      Uncommon                         Fatigue conditions
Rare                             Severe anaphylactic or anaphylactoid reactions (e.g.,
with shock) occurs rarely.
 fever

Malaise
Gastrointestinal disorders                     Uncommon                         dry mouth, thirst, nausea, bowel motility disturbances, vomiting,
diarrhea, constipation10

Rare                             Acute Pancreatitis

Renal and urinary disorders                    Rare                             Interstitial nephritis Acute renal failure
Increased urine production,
Urinary incontinence and urinary obstruction 11
Acute urine retention12

Not known                        Nephrocalcinosis/Nephrolithiasis has been reported in premature infants
Investigations                                 Uncommon                         Blood creatinine increased and Blood urea increased13

Not known                        Transaminases increased (In isolated cases)

Glucose tolerance decreased 14


1
Although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinemia (e.g., in nephritic syndrome) and/or when intravenous furosemide has been given too rapidly.
2
Furosemide may cause a reduction in blood pressure which, if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance.
3
As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy.
Furosemide leads to increased excretion of sodium and chloride and consequently increase excretion of water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased. Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or e.g., where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses.
4
The risk of this abnormality increases at higher dosages and is influenced by the underlying disorder (e.g., cirrhosis of the liver, heart failure), concomitant medication (see section 4.5) and diet.
5
Sodium deficiency can occur; this can manifest itself in the form of confusion, muscle cramps, muscle weakness, loss of appetite, dizziness, drowsiness and vomiting.


6
Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.
7
Magnesium and calcium deficiency result very rarely in tetany and heart rhythm disturbances. Serum calcium levels may be reduced; in very rare cases tetany has been observed.
8
The diuretic action of furosemide may lead to or contribute to hypovolemia and dehydration, especially in elderly patients. Severe fluid depletion may lead to hemoconcentration with a tendency for thromboses to develop.
9
If furosemide is administered to premature infants (including those with respiratory distress syndrome) during the first weeks of life, it may increase the risk of persistent patent ductus arteriosus.
10
Gastro-intestinal disorder such as nausea, malaise or gastric upset (vomiting or diarrhea) and constipation may occur.
but not usually severe enough to necessitate withdrawal of treatment.
11Increased  urine production, urinary incontinence, can be caused or symptoms can be exacerbated in patients with urinary tract obstruction.
12Acute  urine retention, possibly accompanied by complications, can occur for example in patients with bladder disorders, prostatic hyperplasia or narrowing of the urethra.
13Aswith other diuretics, treatment with furosemide may lead to transitory increase in blood creatinine and urea levels.
Serum levels of uric acid may increase, and attacks of gout may occur.
14Glucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control; latent diabetes mellitus may become manifest. Insulin requirements of diabetic patients may increase.
Special population:                                                                                                           1 Patients with hepatic impairment
Pre-existing metabolic alkalosis (e.g., in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.
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 event should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/