DRUG INTERACTIONS

 

No specific drug-drug interaction studies have been performed.

 

BRIEF SUMMARY

 

ABALOPARATIDE- ( Apr- 2017)

 

Indn-      To treat osteoporosis in postmenopausal women at high risk  of fracture or those who other therapies   

 

Comp-      Injection: 3120 mcg/1.56 mL (2000 mcg/mL)  in a  single-patient-use prefilled pen.    Recommended dose is 80 mcg subcutaneously once daily;  patients should receive supplemental calcium and vitamin D  if dietary intake is inadequate. 

 

ADR-     The most common adverse reactions (incidence .2%) are hypercalciuria,

 dizziness, nausea, headache, palpitations, fatigue, upper abdominal

 pain and vertigo. 

 

CI-    None

 

 WARNINGS-

 Orthostatic Hypotension: Instruct patients to sit or lie down if symptoms 

 develop after dose administration. 

 

 Hypercalcemia: 

 Avoid use in patients with pre-existing hypercalcemia and those 

 known to have an underlying hypercalcemic disorder, such as primary 

 hyperparathyroidism.

 

Pat Infn-

 

 

 

 

 

 

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U.S. FDA APPROVED  DRUGS DURING 2017

 

Sr.No-  18

  

Name of the  Drug-        Tymlos

 

Active Ingredient-          Abaloparatide                                                                                                                                                                                                           Pharmacological Classification- 

 

                       To treat osteoporosis in postmenopausal women at high risk

                       of fracture or those who other therapies                

                                                                                                                                                             

Date of Approval-          04-28-2017

 

 (Ref- FDA approved List 2017)                                                                                                                                                                                                                                                                                                                                                                                     HIGHLIGHTS OF PRESCRIBING INFORMATION 

 

These highlights do not include all the information needed to use 

TYMLOS safely and effectively. 

See full prescribing information for TYMLOS.

 

TYMLOS (abaloparatide) i njection, for subcutaneous use

 Initial U.S. Approval: 2017

 

WARNING: 

 RISK OF OSTEOSARCOMA

 

 See full prescribing information for complete boxed warning.

 Abaloparatide caused a dose-dependent increase in the incidence 

 of osteosarcoma, a malignant bone tumor, in male and female rats. 

 

 It is unknown whether TYMLOS will cause osteosarcoma in humans. 

 

Use of TYMLOS is not recommended in patients at increased risk 

for osteosarcoma. 

 

Cumulative use of TYMLOS and parathyroid hormone analogs

 (e.g., teriparatide) for more than 2 years during a patient’s lifetime 

 is not recommended. 

 

  INDICATIONS AND USAGE

 

 TYMLOS is a human parathyroid hormone related peptide [PTHrP(1-34)] 

  analog indicated for the treatment of postmenopausal women with

  osteoporosis at high risk for fracture.

 

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             

 

ADVERSE REACTIONS

 

The most common adverse reactions (incidence .2%) are hypercalciuria,

 dizziness, nausea, headache, palpitations, fatigue, upper abdominal

 pain and vertigo. 

CONTRAINDICATIONS

None

 

 WARNINGS AND PRECAUTIONS

 Orthostatic Hypotension: Instruct patients to sit or lie down if symptoms 

 develop after dose administration. 

 

 Hypercalcemia: 

 Avoid use in patients with pre-existing hypercalcemia and those 

 known to have an underlying hypercalcemic disorder, such as primary 

 hyperparathyroidism. 

 

 Hypercalciuria and Urolithiasis:

 Monitor urine calcium if preexisting hypercalciuria or active urolithiasis

 are suspected. 

 

INDICATIONS AND USAGE

 

 TYMLOS is a human parathyroid hormone related peptide [PTHrP(1-34)] 

  analog indicated for the treatment of postmenopausal women with

  osteoporosis at high risk for fracture.

 

 DOSAGE AND ADMINISTRATION

 

Recommended dose is 80 mcg subcutaneously once daily;

 patients should receive supplemental calcium and vitamin D 

 if dietary intake is inadequate. 

 

 Administer as a subcutaneous injection into periumbilical 

 region of abdomen. 

 

 Administer initially where the patient can sit or lie down in case 

 symptoms of orthostatic hypotension occur. 

 

DOSAGE FORMS AND STRENGTHS

 Injection: 3120 mcg/1.56 mL (2000 mcg/mL)  in a 

 single-patient-use prefilled pen. 

 

 The prefilled pen delivers 30 daily doses of 80 mcg abaloparatide

  in 40 mcL of sterile, clear, colorless solution. 

 

 PATIENT COUNSELING INFORMATION

 

 Advise the patient to read the FDA-approved patient labeling 

(Medication Guide and Instructions for Use).

 

 Risk of Osteosarcoma

 Advise patients that the active ingredient in TYMLOS, abaloparatide, 

 caused a dose-dependent increase in the incidence of osteosarcoma 

 in male  and female rats and that it is unknown whether TYMLOS will cause

 osteosarcoma  in humans.

 

 Instruct patients to promptly report signs and symptoms of possible 

 osteosarcoma such as persistent localized pain or occurrence of a new 

 soft tissue mass that is tender to palpation.

 

 Hypercalcemia

 Advise patients that TYMLOS may cause hypercalcemia and discuss the 

 symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy,

 muscle weakness) 

 

 Instruct patients to promptly report signs and symptoms of hypercalcemia.

 

 Orthostatic Hypotension 

  Advise patients to sit or lie down if they feel lightheaded or have palpitations

  after the injection until their symptoms resolve. If these symptoms persist 

  or worsen, advise patients to consult their healthcare provider before 

  continuing treatment.

 

 Use of TYMLOS Pen Instruct patients and caregivers who administer 

 TYMLOS on how to properly use the TYMLOS pen and to follow sharps

  disposal recommendations.

 

  Advise patients not to share their TYMLOS pen or needles with other 

 patients and not to transfer the contents of the pen to a syringe.

 

 Advise patients that each TYMLOS pen can be used for up to 30 days, 

  and after the 30-day use period, to discard the TYMLOS pen, even if it

  still contains unused solution.

 

 Manufactured in Germany for:

 Radius Health, Inc.

 

 CLINICAL PHARMACOLOGY

 

1. Mechanism of Action

 Abaloparatide is a PTHrP(1-34) analog which acts as an agonist at the PTH1 

 receptor (PTH1R). This results in activation of the cAMP signaling pathway 

  in target cells. 

 In rats and monkeys, abaloparatide had an anabolic effect on bone, 

 demonstrated by increases in BMD and bone mineral content (BMC) that 

 correlated with increases in bone strength at vertebral and/or nonvertebral 

 sites.

 

2. Pharmacodynamics

 Effects on Markers of Bone Turnover

 A dose-finding study of abaloparatide administered once daily for 24 weeks 

 demonstrated a dose-response relationship for BMD and bone formation markers.

 

 Daily administration of TYMLOS to postmenopausal women with osteoporosis

 in clinical studies increased the bone formation marker serum procollagen

 type I N-propeptide (PINP). 

 

 The increase in PINP levels peaked at Month 1 at 93% above baseline then

  decreased slowly over time. The increase in PINP was maintained above 

 baseline throughout the treatment duration.

 

 At Month 18, PINP concentrations were approximately 45% above baseline. 

 The increase in the bone resorption marker serum collagen type I cross-linked

  C-telopeptide (sCTX) peaked at Month 3 at 43% above baseline then 

  decreased to 20% above baseline by Month 18.

 

 Cardiac Electrophysiology

 A 4-way cross-over thorough QT/QTc study was conducted in 55 healthy subjects

  who received single doses of placebo, subcutaneous doses of abaloparatide 

 at 80 mcg and 240 mcg (three times the recommended dose), and moxifloxacin

 400 mg orally. 

 

 Abaloparatide increased heart rate, with a mean peak increase of 15 beats 

 per minute (bpm) and 20 bpm at the first time point (15 minutes) after dosing

 with 80 mcg and 240 mcg, respectively. There were no clinically meaningful

 effects of abaloparatide on QTcI (individually corrected QT intervals) or 

cardiac electrophysiology.

 

3. Pharmacokinetics

 Following seven days of subcutaneous administration of abaloparatide 

 80 mcg, the mean (SD) abaloparatide exposure was 812 (118) pg/mL 

 for C max and 1622 (641) pg·hr/mL for AUC 0-24 .

 

 USE IN SPECIFIC POPULATIONS

 

1. Pregnancy

 Risk Summary 

 TYMLOS is not indicated for use in females of reproductive potential. 

 There are no human data with TYMLOS use in pregnant women to inform

 any drug associated risks. Animal reproduction studies with abaloparatide

 have not been conducted.

 

2. Lactation

  Risk Summary 

 TYMLOS is not indicated for use in females of reproductive potential.

 There is no information on the presence of abaloparatide in human milk,

 the effects on the breastfed infant, or the effects on milk production.

 

3. Pediatric Use

 Safety and effectiveness of TYMLOS have not been established in 

  pediatric patients. TYMLOS is not recommended for use in pediatric

  patients with open epiphyses or hereditary disorders predisposing to 

  osteosarcoma because of an increased baseline risk of osteosarcoma 

 

4. Geriatric Use

 Of the total number of patients in the postmenopausal osteoporosis clinical

  studies of TYMLOS, 82% were age 65 years and over, and 19% were age

 75 years and over.

 

  No overall differences in safety or effectiveness were  observed between

  these subjects and younger subjects, but greater sensitivity of some 

 older individuals cannot be ruled out.

 

5. Renal Impairment

 No dosage adjustment is required for patients with mild, moderate, or 

 severe renal impairment. 

 

 A study of a single dose of TYMLOS 80 mcg  given subcutaneously was

 conducted in subjects with normal renal function  or mild, moderate,

 or severe renal impairment. The maximal concentration  (Cmax ) and 

area under the concentration-time curve (AUC) of abaloparatide 

 increased 1.4-and 2.1-fold, respectively, in subjects with severe renal

 impairment, compared to subjects with normal renal function. 

 

Patients with severe renal impairment may have increased abaloparatide 

 exposure that may increase the risk of adverse reactions; therefore, monitor 

for adverse reactions.

 

 OVERDOSAGE

 In a clinical study, accidental overdose was reported in a patient who received 

 400 mcg in one day (5 times the recommended clinical dose); dosing was 

 temporarily interrupted. 

 

 The patient experienced asthenia, headache, nausea, and vertigo.

  Serum calcium was not assessed on the day of the overdose, but on the 

 following day the patient’s serum calcium was within the normal range. 

 

 The effects of overdose may include hypercalcemia, nausea, vomiting, 

 dizziness, tachycardia, orthostatic hypotension, and headache.

 

 Overdosage Management 

 There is no specific antidote for TYMLOS. Treatment of suspected overdose 

 should include discontinuation of TYMLOS, monitoring of serum calcium and 

 phosphorus, and implementation of appropriate supportive measures, 

 such as hydration.

 

  Based on the molecular weight, plasma protein binding and volume of 

  distribution, abaloparatide is not expected to be dialyzable.