U.S. FDA APPROVED  DRUGS DURING 2020

Sr.No-  2

ADVERSE REACTIONS

Most common adverse reactions (incidence greater than 5%) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dry skin, dysgeusia and headache 

 Exacerbation of Preexisting Inflammatory Bowel Disease (IBD) : Monitor patients with preexisting IBD for flare of disease; discontinue TEPEZZA if IBD worsens 

Hyperglycemia: Monitor glucose levels in all patients; treat hyperglycemia with glycemic control medications

 PATIENT COUNSELING INFORMATION

Embryo-Fetal Toxicity

? Advise females of reproductive potential that TEPEZZA can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy.

? Educate and counsel females of reproductive potential about the need to use effective contraception prior to initiation, during treatment with TEPEZZA and for 6 months after the last dose of TEPEZZA.

Infusion-related reactions

? Advise patients that TEPEZZA may cause infusion reactions that can occur at any time. Instruct patients to recognize the signs and symptoms of infusion reaction and to contact their healthcare provider immediately for signs or symptoms of potential infusion-related reactions.

Exacerbation of Inflammatory Bowel Disease

? Advise patients on the risk of inflammatory bowel disease (IBD) and to seek medical advice immediately if they experience diarrhea, with or without blood or rectal bleeding, associated with abdominal pain or cramping/colic, urgency, tenesmus or incontinence. Hyperglycemia

? Advise patients on the risk of hyperglycemia and, if diabetic, discuss with healthcare provider to adjust glycemic control medications as appropriate. Encourage compliance with glycemic control.

Manufactured by: Horizon Therapeutics Ireland DAC Dublin, Ireland U.S. License No. 2022 Distributed by: Horizon Therapeutics USA, Inc. Lake Forest, IL 60045

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                    Teprotumumab-trbw’s mechanism of action in patients with Thyroid Eye Disease has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling.

2. Pharmacodynamics-                                                                                              No formal pharmacodynamic studies have been conducted with teprotumumab-trbw.

3. Pharmacokinetics-                                                                                                    The pharmacokinetics of teprotumumab-trbw was described by a two compartment population PK model based on data from 40 patients with Thyroid Eye Disease receiving an initial intravenous infusion of 10 mg/kg, followed by infusions of 20 mg/kg TEPEZZA every 3 weeks in two clinical trials.

Following this regimen, the mean (± standard deviation) estimates for steady-state area under the concentration curve (AUC), peak (Cmax), and trough (Ctrough) concentrations of teprotumumab-trbw were 138 (± 34) mg•hr/mL, 632 (± 139) mcg/mL, and 176 (± 56) mcg/mL, respectively.

Distribution-                                                                                                        Following the recommended TEPEZZA dosing regimen, the population PK estimated mean (± standard deviation) for central and peripheral volume of distribution of teprotumumab-trbw were 3.26 (±0.87) L and 4.32 (± 0.67) L, respectively.

The mean (± standard deviation) estimated inter-compartment clearance was 0.74 (± 0.16) L/day.

Elimination-                                                                                                               Following the recommended TEPEZZA dosing regimen, the population PK estimated mean (± standard deviation) for the clearance of teprotumumab-trbw was 0.27 (± 0.08) L/day and for the elimination half-life was 20 (± 5) days.

Metabolism-                                                                                                            Metabolism of teprotumumab-trbw has not been fully characterized. However, teprotumumab-trbw is expected to undergo metabolism via proteolysis.

Specific Populations-                                                                                                 No clinically significant differences in the pharmacokinetics of teprotumumab-trbw were observed following administration of TEPEZZA based on patient’s age (18-80 years), gender, race/ethnicity (103 White, 10 Black, and 3 Asian), weight (46-169 kg), mild to moderate renal impairment (creatinine clearance 30 to 89 mL/min estimated by Cockcroft-Gault Equation), bilirubin levels (2.7-24.3 mcmol/L), aspartate aminotransferase (AST) levels (11-221 U/L), or alanine aminotransferase (ALT) levels (7-174 U/L).

The effect of hepatic impairment on the pharmacokinetics of teprotumumab-trbw is unknown. Drug Interactions No studies evaluating the drug interaction potential of TEPEZZA have been conducted.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis The carcinogenic potential of TEPEZZA has not been evaluated in long-term animal studies. Mutagenesis The genotoxic potential of TEPEZZA has not been evaluated.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary                                                                                   Based on findings in animals and its mechanism of action inhibiting insulin-like growth factor 1 receptor (IGF-1R), TEPEZZA may cause fetal harm when administered to a pregnant woman.

Adequate and well-controlled studies with TEPEZZA have not been conducted in pregnant women.

There are insufficient data with TEPEZZA use in pregnant women to inform any drug associated risks for adverse developmental outcomes.

If the patient becomes pregnant during treatment, TEPEZZA should be discontinued and the patient advised of the potential risk to the fetus. 

The background rate of major birth defects and miscarriage is unknown for the indicated population.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. 

2. Lactation Risk Summary-                                                                                   There is no information regarding the presence of TEPEZZA in human milk, the effects on the breast-fed infant or the effects on milk production.

3. Females and Males of Reproductive Potential-                                           Contraception- Females Based on its mechanism of action inhibiting IGF-1R, TEPEZZA may cause fetal harm when administered to a pregnant woman 

Advise females of reproductive potential to use effective contraception prior to initiation, during treatment with TEPEZZA and for 6 months after the last dose of TEPEZZA.

4. Pediatric Use-                                                                                                    Safety and effectiveness have not been established in pediatric patients. 

5. Geriatric Use-                                                                                                           Of the 171 patients in the two randomized trials, 15% were 65 years of age or older; the number of patients 65 years or older was similar between treatment groups.

No overall differences in efficacy or safety were observed between patients 65 years or older and younger patients (less than 65 years of age). 

OVERDOSAGE                                                                                                            No information is available for patients who have received an overdosage.