Adverse reactions : תופעות לוואי

4.8   Undesirable effects
The frequencies of reported adverse reactions were derived from the medical literature. The safety profile of sodium iodide I-131 differs widely according to the doses administered, while the doses to be administered are dependent on the type of treatment (i.e. treatment of benign or malignant disease). Moreover, the safety profile depends on the cumulative doses administered and the dose regimens which are used. Therefore, the reported adverse reactions were grouped by their occur- rence in treatment of benign or malignant disease, even though the administered doses and dose regimens were usually not indicated in the respective publications and might not have been in line with the posology recommendations in this SPC.
Frequent occurring adverse reactions are: hypothyroidism, transient hyperthyroidism, salivary and lacrimal gland disorders, and local radiation effects. In cancer treatment additionally gastro- intestinal adverse reactions and bone marrow suppression may frequently occur.

The following tables include reported adverse reactions sorted by system organ classes. Symptoms, which are rather secondary to a group-syndrome (e.g. sicca syndrome) are subsumed in parenthesis behind the respective syndrome.

The following table presents how the frequencies are reflected in this section: Very common: ≥10%
Common:             ≥1% and <10%
Uncommon:           ≥0.1% and <1%
Rare:               ≥0.01% and <0.1%
Very rare:          <0.01%
Not known:          No frequency indications found in the medical literature 

Adverse Reactions after Treatment of Benign Disease:

System Organ Class             Symptom                             Frequency Immune system disorders        Anaphylactoid reaction              Not known Permanent hypothyroidism, hy-
Very common pothyroidism
Endocrine disorders             Transient hyperthyroidism          Common Thyreotoxic crisis, thyroiditis,
hypoparathyroidism (blood cal-      Not known cium decreased, tetany)
Endocrine ophthalmopathy            Common
Eye disorders                  (in Graves`disease)
Sicca syndrome                      Not known
Respiratory thoracic and
Vocal cord paralysis               Very rare mediastinal disorders
Skin and subcutaneous dis-
Iodo acne                          Not known orders
Gastrointestinal Disorders      Sialoadenitis                      Common General disorders and ad-
Local swelling                     Not known ministration site conditions

Adverse reactions after Treatment of Malignant Disease:

System Organ Class             Symptom                             Frequency Leukaemia                           Common
Neoplasms benign, malig- nant and unspecified (incl
Solid cancers                       Not known cysts and polyps)

Aplastic anemia, erythropenia,
Very common bone marrow failure
Blood and lymphatic system disorders                      Leukopenia, thrombocytopenia        Common 
Permanent or severe bone mar-
Not known row suppression
Immune system disorders        Anaphylactoid reaction              Not known Thyreotoxic crisis, transient hy-
Rare perthyroidism

Endocrine disorders            Thyroiditis (leucocytosis transi- ent), hypoparathyroidism (blood
Not known calcium decreased, tetany), hypo- thyroidism
Parosmia                            Very common
Nervous system disorders
Brain oedema                        Not known



System Organ Class               Symptom                               Frequency 
Sicca syndrome (conjunctivitis,
Very common dry eyes, nasal dryness)

Eye disorders
Nasolacrimal duct obstruction
Common
(lacrimation increased)


Dyspnoea                              Common
Throat constriction*, Pulmonary fibrosis, respiratory distress, ob-
Respiratory thoracic and structive airways disorder,
mediastinal pneumonitis, tracheitis, vocal
Not known cord dysfunction (vocal cord paralysis, dysphonia,
hoareseness), oropharyngeal pain, stridor
Sialoadenitis (dry mouth, sali- vary gland pain, salivary gland enlargement, dental caries, tooth
Very common loss), radiation sickness syn-
Gastrointestinal Disorders       drome, nausea, ageusia, anosmia,
dysgeusia, decreased appetite
Vomiting                              Common

Gastritis, dysphagia                  Not known

Renal and urinary disor-
Cystitis radiation ders                                                                   Not known 
Reproductive system and          Ovarian failure                       Very common breast disorders
Azoospermia, oligospermia, de-
Reproductive system and creased fertility male, menstrual     Not known breast disorders disorder
Congenital, familial and
Congenital hypothyroidism             Not known genetic disorders
Influenza like illness, headache,
General disorders and ad-                                              Very common fatigue, neck pain ministration site conditions
Local swelling                       Common
*: especially in existing tracheal stenosis

Detailed description of undesirable effects:

Thyroid and parathyroid gland disorders


Dose dependent hypothyroidism may occur as a late consequence of radioiodine treatment of hy- perthyroidism.
This may manifest itself weeks or years after treatment, requiring suitable timed measurement of thyroid function and appropriate thyroid replacement. Hypothyroidism is generally not seen until 6- 12 weeks after sodium iodide I-131 administration.
In treatment of malignant disease hypothyroidism is frequently reported as an adverse reaction, however, radioiodine treatment in malignant disease usually follows thyroidectomy.
The destruction of thyroid follicles caused by the radiation exposure of sodium iodide (I-131) may lead to exacerbation of an already existing hyperthyroidism after 2 – 10 days or even to thyrotoxic crisis. Occasionally, an immune hyperthyroidism may develop after initial normalisation (latency period 2 – 10 months). With high dose radioiodine treatment, the patient may experience transient inflammatory thyroiditis and tracheitis 1-3 days after administration, with a possibility of severe tracheal constriction, especially where there is existing tracheal stenosis.
In rare cases, a temporary hyperthyroidism could be found even after treatment of functional thy- roid carcinoma.
Cases of transient hypoparathyroidism have been observed after radioiodine; they must be moni- tored accordingly and treated with replacement therapy.

Eye disorders
Endocrine ophthalmopathy may progress or new ophthalmopathy may occur after radioiodine ther- apy of hyperthyroidism or Graves` disease.

Local irradiation effects
Vocal cord dysfunction and paralysis have been reported after administration of sodium iodide I- 131, however, in some cases this might also have been caused by thyroid surgery and it cannot be decided whether the dysfunction of the vocal cords was caused by radiation or by surgical treat- ment.
High tissue uptake of radioiodine can be associated with local pain, discomfort and oedema e.g. in case of radioiodine treatment of the remnant thyroid gland, a diffuse and severe soft tissue pain may occur in the head and neck region.
Radiation induced pneumonia and pulmonary fibrosis have been observed in patients with diffuse pulmonary metastases from differentiated thyroid carcinoma, due to destruction of metastatic tis- sue. This occurs mainly after high dose radioiodine therapy.
In the treatment of metastasising thyroid carcinomas with CNS involvement, the possibility of local cerebral oedema and/or an increasing existing cerebral oedema must also be born in mind.

Gastrointestinal disorders
High levels of radioactivity may also lead to gastrointestinal disturbance, usually within the first hours or days after administration. For prevention of gastrointestinal disorders see section 4.4.

Salivary and lacrimal gland disorders
Sialoadenitis may occur, with swelling and pain in the salivary glands, partial loss of taste and dry mouth. Sialoadenitis is usually reversible spontaneously or with antiinflammatory treatment but cases have occasionally been described of dose-dependent persistent ageusia and dry mouth. The lack of saliva may lead to infections, e.g. caries and this may result in loss of teeth. For prevention of salivary disorders see section 4.4.



Malfunction of the salivary and/or lacrimal glands with resulting sicca syndrome may also appear with a delay of several months and up to two years after radioiodine therapy. Although sicca syn- drome is a transient effect in most cases, the symptom may persist for years in some patients.

Bone marrow depression
As a late consequence, reversible bone marrow depression may develop, presenting with isolated thrombocytopenia or erythrocytopenia which may be fatal. Bone marrow depression is more likely to occur after one single administration of more than 5000 MBq, or after repeat administration in intervals below 6 months.

Secondary malignancies
After higher activities, typically those used in the treatment of thyroid malignancies, an increased incidence of leukaemia has been observed.
There is also evidence for an increased incidence of secondary solid cancers at high activi- ties (more than 7.4 GBq).

Fertility impairment
After radioiodine therapy of thyroid carcinoma, a dose dependent impairment of fertility may occur in men and women.

General advice
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary effects. The radiation dose resulting from therapeutic exposure may result in higher inci- dence of cancer and mutations. In all cases it is necessary to ensure that the risks of the radiation are less than those of the disease itself. The radiation dose delivered (EDE) after therapeutic doses of sodium iodide I-131 is higher than 20 mSv.

Paediatric population
Types of adverse reactions in children are expected to be the same as in adults. Based on greater radiation sensitivity of child tissue (see section 11) and the greater life expectancy frequency and severity may be different.