Adverse reactions : תופעות לוואי

4.8    Undesirable effects

The Adverse reaction terms were then categorised utilising the incidence rate as follows: 
Very Common: ≥ 1/10 (>10%)
Common: ≥ 1/100 and < 1/10, (>1% and <10%)
Uncommon: ≥ 1/1000 and < 1/100, (>0.1% and <1%)
Rare: ≥ 1/10,000 and < 1/1000, (>0.01% and <0.1%)
Very Rare: < 1/10,000, (<0.01%)
Not Known

Immune System Disorder
Not Known                                          Anaphylactic reaction Nervous System Disorders
Common                                             Dizziness, headache Gastrointestinal Disorders
Very common                                        Diarrhoea*
Common                                             Abdominal pain*, constipation, dyspepsia, flatulence, nausea, vomiting
Skin and Subcutaneous Tissue Disorders
Very Common                                        Rash
Pregnancy, puerperium, and perinatal conditions

Rare                                                 Uterine rupture** Not Known                                            Amniotic fluid embolism, abnormal uterine contractions, foetal death,
incomplete abortion, premature birth,
retained placenta, uterine perforation
Reproductive System and Breast Disorders
Uncommon                                             Vaginal haemorrhage (including postmenopausal bleeding), intermenstrual bleeding, menstrual disorder uterine cramping
Rare                                                 Menorrhagia, dysmenorrhoea Not Known                                            Uterine haemorrhage Congenital, Familial and Genetic Disorders
Common                                               Foetal malformations General Disorders and Administration Site
Conditions
Not Known                                            Chills
Uncommon                                             Pyrexia
* Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration has been reported.
**Uterine rupture has been uncommonly reported after prostaglandin intake during the second or third trimester of pregnancy. Uterine ruptures occurred particularly in multiparous women or in women with a caesarean section scar.
Diarrhoea can be minimised by using single doses not exceeding 200 micrograms with food and by avoiding the use of predominantly magnesium containing antacids when an antacid is required.

The pattern of adverse events associated with Cytotec® is similar when an NSAID is given concomitantly.

Clinical trials:

In clinical trials, over 15,000 patients and subjects received at least one dose of misoprostol. Adverse reactions involved primarily the gastrointestinal system.

Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration have been reported.

The profile for adverse reactions with >1% incidence was similar for subacute (four to twelve weeks duration) and long- term (up to one year) clinical trials.

The safety of long-term (greater than 12 weeks) administration of misoprostol has been demonstrated in several studies in which patients were treated continuously for up to one year. This includes no adverse or unusual change in the morphology of gastric mucosa, as determined by gastric biopsy.

Special populations:

There were no significant differences in the safety profile of misoprostol in patients who were 65 years of age or older, compared with younger patients.

The use of misoprostol in children under the age of 18 has not been evaluated.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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/