Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions with Qlair when used as an oral contraceptive or in the treatment of heavy menstrual bleeding in women without organic pathology who desire oral contraception are acne, breast discomfort, headache, intracyclic bleeding, nausea and weight increased.

Serious adverse reactions are arterial and venous thromboembolism, which are discussed in section 4.4.

Tabulated list of adverse reactions

The table below reports adverse reactions (ARs) by MedDRA system organ classes (MedDRA SOCs). The most appropriate MedDRA term (version 12.0) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well. The frequencies are based on clinical trial data.
The adverse reactions were recorded in 5 phase III clinical studies (N=2,266 women at risk for pregnancy, N=264 women suffering from dysfunctional uterine bleeding without organic pathology who desire oral contraception) and considered at least possibly causally related to Qlair use. All ADRs listed in the category ‘rare’ occurred in 1 to 2 volunteers resulting in < 0.1%.

N= 2,530 women (100.0%)

System Organ        Common                 Uncommon                  Rare Class               (≥ 1/100 to <1/10)     (≥ 1/1,000 to <1/100)     (≥ 1/10,000 to < 1/1,000) 
Infections and                             Fungal infection          Candidiasis infestations                               Vulvovaginal mycotic      Oral herpes infection1                Pelvic inflammatory
Vaginal infection         disease
Presumed ocular histoplasmosis syndrome
Tinea versicolor
Urinary tract infection
Vaginitis bacterial

Metabolism and                             Increased appetite        Fluid retention nutrition                                                            Hypertriglyceridaemia disorders
Psychiatric                                Depression/depressed      Aggression disorders                                  mood                      Anxiety Emotional disorder2       Dysphoria
Insomnia                  Libido increased
Libido decreased3         Nervousness
Mental disorder           Nightmare
System Organ       Common               Uncommon                Rare Class              (≥ 1/100 to <1/10)   (≥ 1/1,000 to <1/100)   (≥ 1/10,000 to < 1/1,000) 
Mood change4            Restlessness
Sleep disorder
Stress
Nervous system     Headache5            Dizziness               Disturbance in attention disorders                               Migraine6               Paraesthesia Vertigo
Eye disorders                                                   Contact lens intolerance Dry eye
Eye swelling



Cardiac                                                         Myocardial infarction disorders                                                       Palpitations Vascular                                Hot flush               Bleeding varicose vein disorders                               Hypertension            Venous thromboembolism (VTE)
Arterial thromboembolism (ATE)
Hypotension
Phlebitis superficialis
Vein pain
Gastrointestinal   Abdominal pain7      Diarrhoea               Constipation disorders          Nausea               Vomiting                Dry mouth Dyspepsia
Gastrooesophageal reflux disease
Hepatobiliary                           Liver enzymes           Focal nodular disorders                               increased8              hyperplasia of the liver Cholecystitis chronic

Skin and           Acne9                Alopecia                Allergic skin reaction12 subcutaneous                            Hyperhidrosis           Chloasma tissue disorders                        Pruritus10              Dermatitis Rash11                  Hirsutism
Hypertrichosis
Neurodermatitis
Pigmentation disorder
Seborrhoea
Skin disorder13
Musculoskeletal                         Muscle spasms           Back pain System Organ        Common                 Uncommon                    Rare Class               (≥ 1/100 to <1/10)     (≥ 1/1,000 to <1/100)       (≥ 1/10,000 to < 1/1,000)  and connective                                                         Pain in jaw tissue disorders                                                       Sensation of heaviness 
Renal and                                                              Urinary tract pain urinary disorders
Reproductive        Amenorrhea             Breast enlargement16        Abnormal withdrawal system and          Breast discomfort14    Breast mass                 bleeding breast disorders    Dysmenorrhoea          Cervical dysplasia          Benign breast neoplasm Intracyclic bleeding   Dysfunctional uterine       Breast cancer in situ (Metrorrhagia)15       bleeding                    Breast cyst
Dyspareunia                 Breast discharge
Fibrocystic breast          Cervical polyp disease                     Cervix erythema
Menorrhagia                 Coital bleeding
Menstrual disorder          Galactorrhea
Ovarian cyst                Genital discharge
Pelvic pain                 Hypomenorrhoea
Premenstrual syndrome       Menstruation delayed
Uterine leiomyoma           Ovarian cyst ruptured
Uterine spasm               Vaginal odour
Uterine/vaginal             Vulvovaginal burning bleeding incl. spotting17   sensation
Vaginal discharge           Vulvovaginal discomfort
Vulvovaginal dryness
Blood and                                                              Lymphadenopathy lymphatic system disorders
Respiratory,                                                           Asthma thoracic and                                                           Dyspnoea mediastinal                                                            Epistaxis disorders
General                                    Fatigue                     Chest pain disorders and                              Irritability                Malaise administration                             Oedema 18                   Pyrexia site conditions
Investigations      Weight increased       Weight decreased         Smear cervix abnormal Blood pressure changes19
1 including vulvovaginal candidiasis and fungus cervical specimen identified 2 including crying and affect lability
3 including loss of libido
4 including mood altered and mood swings
5 including tension headache and sinus headache
6 including migraine with aura and migraine without aura
7 including abdominal distension, abdominal pain upper and abdominal pain lower 8 including alanine aminotransferase increased, aspartate aminotransferase increased and gamma-glutamyltransferase increased
9 including acne pustular
10 including pruritus generalized and rash pruritic
11 including rash macular
12 including dermatitis allergic and urticaria
13 including skin tightness
14 including breast pain, breast tenderness, nipple disorder and nipple pain 15 including menstruation irregular
16 including breast swelling
17 including vaginal hemorrhage, genital hemorrhage and uterine hemorrhage 18 including oedema peripheral
19 including blood pressure increased and blood pressure decreased


Description of selected adverse reactions
An increased risk of arterial and venous thrombotic and thrombo-embolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in section 4.4.

Occurrence of amenorrhea and intracyclic bleeding based on patient diaries is summarized in section 4.4 Cycle control.

The following serious adverse events have been reported in women using COCs, which are discussed in section 4.4 Special warning and precautions for use: 
Tumours
− The frequency of diagnosis of breast cancer is very slightly increased among COC users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with COC use is unknown. For further information, see sections 4.3 and 4.4; − Liver tumours;


Other conditions
− Erythema nodosum, Erythema multiforme;
− Breast discharge;
− Hypertension;
− Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn’s disease, ulcerative colitis, epilepsy, migraine, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis,
Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice; −   In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema;
−   Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.
−   Chloasma;
−   Hypersensitivity (including symptoms such as rash, urticaria); 

Interactions

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with oral contraceptives (see section 4.5).


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