U.S. FDA APPROVED  DRUGS DURING 2020

Sr.No-  38

ADVERSE REACTIONS

 Adverse reactions - 2% of patients treated with SOGROYA are: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, blood creatine phosphokinase increase, weight increase, anemia 

+ Intracranial Hypertension (IH): Has been reported usually within 8 weeks of initiation. Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with SOGROYA, stop treatment 

+ Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention 

+ Fluid Retention: May occur in adults and may be dose dependent 

+ Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism 

+ Hypothyroidism: Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of SOGROYA. 

+ Pancreatitis: Has been reported; consider pancreatitis in patients with persistent severe abdominal pain 

+ Lipohypertrophy/lipoatrophy: May occur if SOGROYA administered in the same location over a long period of time. Rotate injection sites on a regular basis 

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Neoplasms – Advise patients to report marked changes in skin pigmentation or changes in the appearance of pre-existing nevi.

 Fluid Retention - Advise patients that fluid retention during SOGROYA replacement therapy may frequently occur. Inform patients of the clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) and to report to their healthcare provider any of these signs or symptoms occur during treatment with SOGROYA.

 Pancreatitis - Advise patients that pancreatitis may develop and to report to their healthcare provider any new onset abdominal pain.

 Hypoadrenalism - Advise patients who have or who are at risk for corticotropin deficiency that hypoadrenalism may develop and to report to their healthcare provider if they experience hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss.

 Hypothyroidism - Advise patients/caregivers that undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. Advise patients/caregivers they may require periodic thyroid function tests.

 Intracranial Hypertension - Advise patients to report to their healthcare provider any visual changes, headache, and nausea and/or vomiting.

 Hypersensitivity Reactions – Advise patients that serious systemic hypersensitivity reactions (anaphylaxis and angioedema) are possible and that prompt medical attention should be sought if an allergic reaction occurs.

 Glucose Intolerance/ Diabetes Mellitus – Advise patients that new onset pre- /diabetes mellitus or exacerbation of preexisting diabetes mellitus can occur and monitoring of blood glucose during treatment with SOGROYA may be needed.

 Lipohypertrophy/ Lipoatrophy – Advise patients that lipohypertrophy or lipoatrophy can occur if SOGROYA is administered subcutaneously at the same site over a long period of time. Advise patients to rotate injection sites when administering SOGROYA to reduce this risk.

Novo Nordisk® is a registered trademark of Novo Nordisk A/S. SOGROYA® is a registered trademark of Novo Nordisk Health Care AG. © 2002-2020 Novo Nordisk Health Care AG PATENT INFORMATION: http://novonordisk-us.com/products/product-patents.html For information contact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, New Jersey 08536 1-888-668-6444

Manufactured by: Novo Nordisk Inc. Plainsboro, NJ 08536 U.S. License No. 1261

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                  Somapacitan-beco binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects.

2. Pharmacodynamics- IGF-I was measured to assess the pharmacodynamic (PD) properties of somapacitan-beco. Somapacitan-beco normalizes the mean IGF-I standard deviation score (SDS) level from a baseline value below -2 to a value within the reference range (-2 to +2) in treatment-naïve adult patients with GHD 

3. Pharmacokinetics

The pharmacokinetics (PK) of somapacitan-beco following subcutaneous administration have been investigated at clinically relevant doses (e.g., 0.01 to 0.32 mg/kg in healthy adults, and 0.02 to 0.12 mg/kg in adults with GHD).

Absorption-                                                                                                                         In adults with GHD, a maximum concentration of somapacitan-beco is reached 4 to 24 hours post dose. Steady state exposure is achieved following 1 to 2 weeks of once weekly administration of subcutaneous somapacitan-beco.

Distribution-                                                                                                             Somapacitan-beco is extensively bound (>99%) to plasma proteins.

Based on population PK analyses, the estimated volume of distribution (V/F) of somapacitan-beco in adult GHD patients is approximately 14.6 L.

Elimination-                                                                                                                        The plasma elimination half-life of somapacitan-beco is approximately 2 to 3 days. Metabolism: Somapacitan-beco is metabolized via proteolytic cleavage of the linker sequence between the peptide backbone and albumin binder sidechain.

Excretion:                                                                                                                           The primary excretion routes of somapacitan-beco-related material are via the urine and feces. Approximately 81% of the dose is excreted in the urine and approximately 13% is excreted in the faces.

Specific Populations-                                                                                                    Body weight:  The exposure of somapacitan-beco decreases with increasing body weight. However, the somapacitan-beco dose range of 0.1 to 8 mg/week provides adequate systemic exposure to reach target IGF-1 levels over the weight range of 34.5-150.5 kg evaluated in the clinical trials.

Geriatric patients:                                                                                                           Adult patients greater than 65 years of age and geriatric patients have a higher exposure than younger subjects at the same somapacitan-beco dose.

Female patients receiving estrogen:                                                                          Female patients and in particular female patients on oral estrogen, have lower exposure than males at the same somapacitan-beco dose 

Hepatic impairment:                                                                                                          A somapacitan-beco dose of 0.08 mg/kg at steady state resulted in comparable somapacitan-beco exposure between patients with normal hepatic function and mild hepatic impairment (Child-Pugh A).

Renal impairment:                                                                                                             In general, somapacitan-beco exposure tended to increase with decreasing estimated glomerular filtration rate. A somapacitan-beco dose of 0.08 mg/kg at steady state resulted in higher exposures in patients with renal impairment, that was most pronounced for patients with severe renal impairment and patients requiring haemodialysis (AUC0-168h ratios to normal renal function were 1.75 and 1.63, respectively).

USE IN SPECIFIC POPULATIONS

Pregnancy Risk Summary-                                                                                            There are no available data on SOGROYA use in pregnant women; however, published studies with short-acting recombinant growth hormone (rhGH) use in pregnant women over several decades have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

The estimated background risk of 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 2-4% and 15-20%, respectively. 

2.Lactation Risk Summary-                                                                                               There is no information on with the presence of somapacitan-beco in human milk, the effects on the breastfed infant, or the effects on milk production. Somapacitan-beco-related material was secreted into milk of lactating rats.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SOGROYA and any potential adverse effects on the breastfed infant from SOGROYA or from the underlying maternal condition.

3.Pediatric Use                                                                                                                  The safety and effectiveness of SOGROYA have not been established in pediatric patients.

Risks in pediatric patients associated with growth hormone use include:                             x Sudden death in pediatric patients with Prader-Willi Syndrome                                     x Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head x Slipped capital femoral epiphysis                                               x Progression of preexisting scoliosis                                                                                 x Pancreatitis

4.Geriatric Use-                                                                                                                   In clinical studies a total of 52 (15.6%) of the 333 SOGROYA-treated patients were 65 years or older and 3 (0.9%) were 75 years or older .

 Subjects older than 65 years appeared to have higher exposure than younger subjects at the same dose level. Elderly patients may be more sensitive to the action of somapacitan-beco, and therefore may be at increased risk for adverse reactions.

Initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose 

5.Hepatic Impairment-                                                                                                     No specific dose adjustment of SOGROYA is required for patients with mild hepatic impairment.

Higher somapacitan-beco exposure was observed in patients with moderate hepatic impairment.

In patients with moderate hepatic impairment, initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose. The maximum dose should not exceed 4 mg once weekly.

DRUG ABUSE AND DEPENDENCE -                                                                 Controlled Substance SOGROYA contains somapacitan-beco, which is not a controlled substance.

Abuse Inappropriate use of SOGROYA may result in significant negative health consequences. Dependence SOGROYA is not associated with drug related withdrawal adverse reactions.

OVERDOSAGE-                                                                                                             Acute overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia.

Overdose with SOGROYA is likely to cause fluid retention.

Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess endogenous growth hormone.