Adverse reactions : תופעות לוואי

6      ADVERSE REACTIONS
6.1    Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to THYROGEN in 481 thyroid cancer patients who participated in a total of 6 clinical trials of THYROGEN: 4 trials for diagnostic use and 2 trials for ablation. In clinical trials, patients had undergone near- total thyroidectomy and had a mean age of 46.1 years. Thyroid cancer diagnosis was as follows: papillary (69.2%), follicular (12.9%), Hurthle cell (2.3%) and papillary/follicular (15.6%). Most patients received 2 intramuscular injections of 0.9 mg of THYROGEN injections given 24 hours apart [see Clinical Studies (14.1,14.2)].
The safety profile of patients who have undergone thyroidectomy and received THYROGEN as adjunctive treatment for radioiodine ablation of thyroid tissue remnants for well-differentiated thyroid cancer did not differ from that of patients who received THYROGEN for diagnostic purposes.
Reactions reported in ≥ 1% of patients in the combined trials are summarized in Table 1.
In some studies, an individual patient may have participated in both THYROGEN and thyroid hormone withdrawal [see Clinical Studies (14.1,14.2)].
Table 1: Summary of Adverse Reactions by THYROGEN and Thyroid Hormone Withdrawal in Pooled Clinical Trials (≥1% of Patients in any Phase) THYROGEN                  Thyroid Hormone
Withdrawal
(N=481)                    (N=418)
Preferred Term                          n (%)                      n (%) Nausea                                  53 (11)                    2 (<1) Headache                                 29 (6)                       0 Fatigue                                  11 (2)                    2 (<1) Vomiting                                 11 (2)                       0 Dizziness                                 9 (2)                    0 (0.0) Asthenia                                  5 (1)                    1 (<1) 6.2      Postmarketing Experience
The following adverse reactions have been identified during postapproval use of THYROGEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
•     Transient (<48 hours) influenza-like symptoms, including fever (>100°F/38°C), chills/shivering, myalgia/arthralgia, fatigue/asthenia/malaise, headache, and chills.
•     Hypersensitivity including urticaria, rash, pruritus, flushing, and respiratory signs and symptoms.
•     Injection site reactions, including pain, erythema, bruising, and pruritus.
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/
8        USE IN SPECIFIC POPULATIONS
8.1      Pregnancy
Risk Summary
THYROGEN may be used in combination with radioiodine (RAI). If THYROGEN is administered with RAI, the combination regimen is contraindicated in pregnant women because fetal exposure to RAI can lead to neonatal hypothyroidism, which in some cases is severe and irreversible. Refer to the RAI prescribing information for more information on use during pregnancy.
Available data from case reports and postmarketing experience with THYROGEN use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Animal reproduction studies have not been conducted with THYROGEN.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2      Lactation
Risk Summary
The concomitant use of THYROGEN and therapeutic radioiodine (RAI) is contraindicated in lactating women because RAI concentrates in the breast tissue and increases the risk of radiation breast toxicity (refer to the therapeutic RAI Prescribing Information).
If THYROGEN is administered with RAI for diagnostic use, discontinue breastfeeding after RAI administration because of the potential for serious adverse reactions from RAI in the breastfed infant (refer to the diagnostic RAI Prescribing Information).
If THYROGEN is not administered with RAI, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for THYROGEN and any potential adverse effects on the breastfed child from THYROGEN or from the underlying maternal condition.
There are no available data on the presence of thyrotropin alfa in human milk, the effects on the breastfed infant, or the effects on milk production.
8.3    Females and Males of Reproductive Potential
THYROGEN may be used in combination with radioiodine (RAI). If THYROGEN is administered with RAI, the information for RAI regarding pregnancy testing, contraception, and infertility also applies to the combination regimen. Refer to the RAI prescribing information for additional information.
8.4    Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5    Geriatric Use
In pooled clinical studies of THYROGEN, 60 patients (12%) were >65 years, and 421 (88%) were ≤ 65 years of age. Results from controlled trials do not indicate a difference in the safety and efficacy of THYROGEN between adult patients less than 65 years and those over 65 years of age [see Warnings and Precautions (5.1)].
8.6    Renal Impairment
Elimination of THYROGEN is significantly slower in dialysis-dependent end- stage renal disease (ESRD) patients, resulting in prolonged elevation of TSH levels.