ZOTIDE Injection (Teriparatide)

Table of Content

The currently available pharmacological treatments for osteoporosis are predominantly anti-resorptive. These inhibit osteoclast-mediated bone loss and therefore reduce bone turnover, and increase BMD because bone formation is permitted and bone resorption is inhibited.

Teriparatide is a first in class, anabolic agent with a unique mechanism that results in increased bone formation.

ZOTIDE cartridge contains teriparatide which is a biosynthetic (rDNA origin) peptide fragment of the human parathyroid hormone (PTH). It is produced by using a strain of Escherichia coli employing recombinant DNA technology. Its sequence is identical to that of 34 N-terminal amino acids (the biological active region) of the endogenous 84-amino acid human parathyroid hormone.

ZOTIDE is indicated for treatment of patients with severe osteoporosis. Once-daily subcutaneous administration of teriparatide increases apposition of new bone on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity.

ZOTIDE cartridge is to be used to with ZOTIDE Delivery Device Pen and ZOTIDE Pen Needles only.

zoti

For the use of a Registered Medical Practitioner or Hospital or a Laboratory only   

Qualitative And Quantitative Composition

ZOTIDE

Each cartridge contains:

Teriparatide ……………………. 750 mcg/3 ml

Water for injection, IP……q.s.

Excipients: Glycerol IP, Succinic acid, Meta-cresol, Sodium hydroxide IP

Dosage Form(S) And Strength(S)

Injection (Multi-dose cartridge for subcutaneous injection containing 28 doses) containing teriparatide 750 mcg/3ml.

Clinical Particulars

Therapeutic Indication

ZOTIDE is indicated for the treatment of patients with severe osteoporosis. 

Posology and Method of Administration

ZOTIDE cartridge should be used with the ZOTIDE Delivery Device-Pen and ZOTIDE Pen Needles. The recommended dose of ZOTIDE is 80 µl containing 20 mcg teriparatide to be administered once daily by subcutaneous injection in the thigh or abdomen. There are no data available on the safety or efficacy of intravenous or intramuscular injection of ZOTIDE. ZOTIDE should be administered initially in an environment in which the patient can assume a supine or sitting position if orthostatic hypotension should occur.

ZOTIDE is a clear and colourless liquid. Do not use if solid particles appear or if the solution is cloudy or coloured. Patients and caregivers who administer ZOTIDE should receive appropriate training and instruction on the proper use of the ZOTIDE delivery device from a qualified health professional.

Use of ZOTIDE for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.

Following cessation of ZOTIDE therapy, the patients may be continued on other osteoporosis therapy.

Contraindications

  • Hypersensitivity to teriparatide or any of the excipients of this product. Reactions have included angioedema and anaphylaxis
  • Pregnancy and breast-feeding
  • Pre-existing hypercalcaemia
  • Severe renal impairment  
  • Metabolic bone diseases (including hyperparathyroidism and Paget’s disease of the bone) other than primary osteoporosis or glucocorticoid-induced osteoporosis
  • Unexplained elevations of alkaline phosphatase
  • Prior external beam or implant radiation therapy to the skeleton
  • Patients with skeleton malignancies or bone metastases should be excluded from treatment with teriparatide 

Special Warnings and Precautions for Use

Osteosarcoma

An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with teriparatide. Osteosarcoma has been reported in patients treated with teriparatide in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use. Avoid teriparatide use in patients with (these patients are at increased baseline risk of osteosarcoma):

Open epiphyses (pediatric and young adult patients) (teriparatide is not approved in pediatric patients).

Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone.

Bone metastases or a history of skeletal malignancies.

Prior external beam or implant radiation therapy involving the skeleton.

Hereditary disorders predisposing to osteosarcoma.

Treatment Duration

Use of teriparatide for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture

Bone Metastases and Skeletal Malignancies

Patients with bone metastases or a history of skeletal malignancies should not be treated with teriparatide.

Metabolic Bone Diseases

Patients with metabolic bone diseases other than osteoporosis should not be treated with teriparatide.

Orthostatic Hypotension

Teriparatide should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur. In short-term clinical pharmacology studies with teriparatide, transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients. Typically, an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours. When transient orthostatic hypertension occurred, it happened within the first several doses, was relieved by placing subjects in a reclining position, and did not preclude continued treatment.

Urolithiasis or Pre-existing Hypercalciuria

In clinical trials, the frequency of urolithiasis was similar in patients treated with teriparatide and placebo Teriparatide has not been studied in patients with active urolithiasis in reported clinical trials. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered.

Teriparatide should be used with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

Hypercalcaemia and Hypercalcaemic Disorders

In normo-calcaemic patients, slight and transient elevations of serum calcium concentrations have been observed following teriparatide injection. Serum calcium concentrations reach a maximum between 4 and 6 hours and return to baseline by 16 to 24 hours after each dose of teriparatide. Therefore, if any blood samples are taken from a patient, this should be done at least 16 hours after the most recent teriparatide injection. Routine calcium monitoring during the therapy is not required.  

Teriparatide has not been studied in patients with pre-existing hypercalcemia. These patients should not be treated with teriparatide because of the possibility of exacerbating hypercalcemia. Patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, should not be treated with teriparatide.

Teriparatide may cause small increases in the urinary calcium excretion, but the incidence of hypercalciuria did not differ from that in the placebo-treated patients in clinical trials.

Risk of Cutaneous Calcification Including Calciphylaxis

Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking teriparatide.

Risk factors for development of calciphylaxis include underlying auto-immune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue teriparatide in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification.

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Drug Interactions

Digoxin

In a study of 15 healthy people administered digoxin daily to the steady state, a single dose of teriparatide did not alter the effect of digoxin on the systolic time interval (from electrocardiographic Q-wave onset to aortic valve closure, a measure of digoxin’s calcium-mediated cardiac effect). However, sporadic case reports have suggested that hypercalcaemia may predispose patients to digitalis toxicity. Because teriparatide transiently increases serum calcium, teriparatide should be used with caution in patients taking digitalis.

Hydrochlorothiazide

The coadministration of hydrochlorothiazide 25 mg with teriparatide did not affect the serum calcium response to teriparatide 40 mcg. The 24-hour urine excretion of calcium was reduced by a clinically unimportant amount (15%). The effect of coadministration of a higher dose of hydrochlorothiazide with teriparatide on serum calcium levels has not been studied.

Furosemide

Coadministration of intravenous furosemide (20 to 100 mg) with teriparatide 40 mcg in healthy people and patients with mild, moderate, or severe renal impairment (CrCl 13 to 72 mL/min) resulted in small increases in the serum calcium (2%) and 24-hour urine calcium (37%) responses to teriparatide that did not appear to be clinically important.

Use in Special Population

Renal Impairment

In 5 patients with severe renal insufficiency (CrCl< 30 ml/min), the AUC and T1/2 of teriparatide was increased by 73% and 77%, respectively. Maximum serum concentration of teriparatide was not increased. Caution should be exercised in patients with moderate renal impairment.

Hepatic Impairment

No studies have been reported in patients with hepatic impairment.

Pregnancy

Pregnancy Category C

Teriparatide is contraindicated for use during pregnancy. There are no adequate and well-controlled studies of teriparatide in pregnant women. In animal studies, teriparatide increased skeletal deviations and variations in mouse offspring at doses more than 60 times the equivalent human dose and produced mild growth retardation and reduced motor activity in rat offspring at doses more than 120 times the equivalent human dose. Teriparatide should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

In animal studies, pregnant mice received teriparatide during organogenesis at subcutaneous doses 8 to 267 times the human dose. At doses ≥ 60 times the human dose, the foetuses showed an increased incidence of skeletal deviations or variations (interrupted rib, extra vertebra or rib). When pregnant rats received subcutaneous teriparatide during organogenesis at doses 16 to 540 times the human dose, the foetuses showed no abnormal findings.

In a perinatal/postnatal study, pregnant rats received subcutaneous teriparatide from organogenesis through lactation. Mild growth retardation in female offspring at doses ≥120 times the human dose (based on surface area, mcg/m2). Mild growth retardation in male offspring and reduced motor activity in both male and female offspring occurred at maternal doses 540 times the human dose. There were no developmental or reproductive effects in mice or rats at doses 8 or 16 times the human dose, respectively. Exposure multiples were normalized based on body surface area (mcg/m2). Actual animal doses: mice (30 to 1000 mcg/kg/day); rats (30 to 1000 mcg/kg/day).

Lactation

Teriparatide is contraindicated for use during breast-feeding. However, it is not known whether teriparatide is excreted in human milk. Because of the potential for tumorigenicity shown for teriparatide in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Women of childbearing potential / Contraception in females

Women of childbearing potential should use effective methods of contraception during use of teriparatide. If pregnancy occurs, teriparatide should be discontinued.

Paediatric Use

The safety and efficacy of teriparatide have not been established in any paediatric population. Teriparatide should not be prescribed in patients at an increased baseline risk of osteosarcoma which include paediatric and young adult patients with open epiphyses. Therefore, teriparatide is not indicated for use in paediatric or young adult patients with open epiphyses.

Geriatric Use

Dosage adjustment based on age is not required. In a clinical trial, no overall differences in safety or effectiveness were observed between elderly subjects (>65 years) and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Effects on Ability to Drive and Use Machines

Teriparatide has no or negligible influence on the ability to drive and use machines. However, transient, orthostatic hypotension or dizziness was observed in some patients. These patients should refrain from driving or the use of machines until symptoms have subsided.

Undesirable Effects

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The most commonly reported adverse reactions in patients treated with teriparatide are nausea, pain in limb, headache and dizziness.

The adverse reactions associated with the use of teriparatide in osteoporosis clinical trials and post-marketing exposure are summarised in the table below. The following convention has been used for the classification of adverse reactions: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000).

Blood and Lymphatic System Disorders

Common: Anaemia

Immune System Disorder

Rare: Anaphylaxis

Metabolism and Nutrition Disorders

Common: Hypercholesterolaemia

Uncommon: Hypercalcaemia greater than 2.76 mmol/L, hyperuricaemia

Rare: Hypercalcaemia greater than 3.25 mmol/L

Psychiatric Disorders

Common: Depression

Nervous System Disorders

Common: Dizziness, headache, sciatica, syncope, insomnia

Ear and Labyrinth Disorders

Common: Vertigo

Cardiac Disorders

Common: Palpitations

Uncommon: Tachycardia

Vascular Disorders

Common: Hypotension, hypertension, angina pectoris

Respiratory, Thoracic and Mediastinal Disorders

Common: Dyspnoea, rhinitis, cough increased, pharyngitis, pneumonia

Uncommon: Emphysema

Gastrointestinal Disorders

Common: Nausea, vomiting, hiatus hernia, gastro-oesophageal reflux disease, constipation, diarrhea, dyspepsia, gastrointestinal disorder

Uncommon: Haemorrhoids

Skin and Subcutaneous Tissue Disorders

Common: Sweating increased, rash

Musculoskeletal and Connective Tissue Disorders

Very common: Pain in limb

Common: Muscle cramps, neck pain

Uncommon: Myalgia, arthralgia, back cramp/pain*

Renal and Urinary Disorders

Uncommon: Urinary incontinence, polyuria, micturition urgency, nephrolithiasis

Rare: Renal failure/impairment

General Disorders and Administration Site Conditions

Common: Fatigue, chest pain, asthenia, mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritus and minor bleeding at injection site

Uncommon: Injection site erythema, injection site reaction

Rare: Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalised urticaria, chest pain, oedema (mainly peripheral)

Investigations

Uncommon: Weight increased, cardiac murmur, alkaline phosphatase increase

Description of Selected Adverse Reactions

In clinical trials the following reactions were reported at a ≥ 1 % difference in frequency from placebo: vertigo, nausea, pain in limb, dizziness, depression, dyspnoea.

Teriparatide increases serum uric acid concentrations. In clinical trials, 2.8 % of teriparatide patients had serum uric acid concentrations above the upper limit of normal compared with 0.7 % of placebo patients. However, the hyperuricaemia did not result in an increase in gout, arthralgia, or urolithiasis.

In a large clinical trial, antibodies that cross-reacted with teriparatide were detected in 2.8 % of women receiving teriparatide. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no evidence of hypersensitivity reactions, allergic reactions, effects on serum calcium, or effects on Bone Mineral Density (BMD) response.

Teriparatide increased serum uric acid concentrations. In clinical trials, 3% of teriparatide patients had serum uric acid concentrations above the upper limit of normal compared with 1% of placebo patients. However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis.

No clinically important adverse renal effects were observed in clinical studies. Assessments included creatinine clearance; measurements of blood urea nitrogen (BUN), creatinine, and electrolytes in serum; urine specific gravity and pH; and examination of urine sediment.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of teriparatide. 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.

Osteosarcoma: Cases of bone tumor and osteosarcoma have been reported rarely in the postmarketing period. The causality to teriparatide use is unclear.

Hypercalcemia: Hypercalcemia greater than 13.0 mg/dL has been reported with teriparatide use.

Adverse events reported since market introduction that were temporally (but not necessarily causally) related to teriparatide therapy include the following:

Allergic Reactions: Anaphylactic reactions, drug hypersensitivity, angioedema, urticaria

Investigations: Hyperuricemia

Respiratory System: Acute dyspnea, chest pain

Musculoskeletal: Muscle spasms of the leg or back

Other: Injection site reactions including injection site pain, swelling and bruising; oro-facial edema

If you experience any side effects, talk to your doctor or pharmacist. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024.  

By reporting side effects, you can help provide more information on the safety of this product.

Overdose

Incidents of overdose in humans have not been reported in clinical trials.

Signs and Symptoms

Teriparatide has been administered in single doses of up to 100 mcg and in repeated doses of up to 60 mcg/ day for 6 weeks. The effects of overdosage that might be expected include delayed hypercalcaemia and risk of orthostatic hypotension. Nausea, vomiting, dizziness and headache can also occur.

Overdose Management

There is no specific antidote for teriparatide. Treatment of suspected overdose should include transitory discontinuation of teriparatide, monitoring of serum calcium, and implementation of appropriate supportive measures such as hydration. 

Overdose Experience Based on Post-marketing Spontaneous Reports

In post-marketing spontaneous reports, there have been cases of medication error where the entire contents (up to 800 mcg) of the teriparatide pen have been administered as a single dose. Transient events reported have included nausea, weakness/lethargy and hypotension. In some cases, no adverse events occurred as a result of the overdose. No fatalities associated with overdose have been reported.

Pharmacological Properties

Mechanism of Action

Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidneys. Teriparatide is the active fragment (1–34) of endogenous human parathyroid hormone. Physiological actions of PTH include stimulation of bone formation by direct effects on bone-forming cells (osteoblasts), indirectly increasing the intestinal absorption of calcium and increasing the tubular reabsorption of calcium and excretion of phosphate by the kidneys. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

Pharmacodynamic Properties

Teriparatide is a bone formation agent to treat osteoporosis. The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide increases apposition of new bone on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity.

When teriparatide 20 mcg is administered once daily, the serum calcium concentration increases transiently, beginning approximately 2 hours after dosing and reaching a maximum concentration between 4 and 6 hours (median increase, 0.4 mg/dL). The serum calcium concentration begins to decline approximately 6 hours after dosing and returns to baseline by 16 to 24 hours after each dose.

Pharmacokinetic Properties

Absorption

Teriparatide is absorbed after subcutaneous injection; the absolute bioavailability is approximately 95% based on pooled data from 20-, 40-, and 80- mcg doses. The rates of absorption and elimination are rapid. The peptide reaches peak serum concentrations about 30 minutes after subcutaneous injection of a 20-mcg dose and declines to non-quantifiable concentrations within 3 hours.

Distribution

The volume of distribution is approximately 1.7 L/kg. The half-life of teriparatide is approximately 1 hour when administered subcutaneously, which reflects the time required for absorption from the injection site.

Systemic clearance of teriparatide (approximately 62 L/hr in women and 94 L/hr in men) exceeds the rate of normal liver plasma flow, consistent with both hepatic and extra-hepatic clearance. Volume of distribution, following intravenous injection, is approximately 0.12 L/kg. Intersubject variability in systemic clearance and volume of distribution is 25% to 50%. The half-life of teriparatide in serum is 5 minutes when administered by intravenous injection and approximately 1 hour when administered by subcutaneous injection. The longer half-life following subcutaneous administration reflects the time required for absorption from the injection site.

Metabolism

No metabolism or excretion studies with teriparatide have been reported but the peripheral metabolism of the parathyroid hormone is believed to occur predominantly in the liver and kidneys.

Excretion

Teriparatide is eliminated through hepatic and extra-hepatic clearance (approximately 62 l/hr in women and 94 l/hr in men).

Special Population

Paediatric Patients

Pharmacokinetic data in pediatric patients are not available.

Geriatric Patients

No age-related differences in teriparatide pharmacokinetics were detected (range 31 to 85 years). Dosage adjustment based on age is not required.

Gender

Although systemic exposure to teriparatide was approximately 20% to 30% lower in men than women, the recommended dose for both genders is 20 mcg/day.

Race

The populations included in the pharmacokinetic analyses were 98.5% Caucasian. The influence of race has not been determined.

Renal Impairment

No pharmacokinetic differences were identified in 11 patients with mild or moderate renal impairment administered a single dose of teriparatide. In 5 patients with severe renal impairment (CrCl<30 mL/min), the AUC and t1/2 of teriparatide were increased by 73% and 77%, respectively. Maximum serum concentration of teriparatide was not increased. No studies have been performed in patients undergoing dialysis for chronic renal failure.

Hepatic Impairment

No studies have been performed in patients with hepatic impairment. Nonspecific proteolytic enzymes in the liver (possibly Kupffer cells) cleave PTH (1-34) and PTH (1-84) into fragments that are cleared from the circulation mainly by the kidney.

Nonclinical Properties

Animal Toxicology or Pharmacology

In single-dose rodent studies using subcutaneous injection of teriparatide, no mortality was seen in rats given doses of 1000 mcg/kg (540 times the human dose based on surface area, mcg/m2) or in mice given 10,000 mcg/kg (2700 times the human dose based on surface area, mcg/m2).

In a long-term study, skeletally mature ovariectomized female monkeys (N=30 per treatment group) were given either daily subcutaneous teriparatide injections of 5 mcg/kg or vehicle. Following the 18-month treatment period, the monkeys were removed from teriparatide treatment and were observed for an additional 3 years. The 5 mcg/kg dose resulted in systemic exposures that were approximately 6 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Bone tumors were not detected by radiographic or histologic evaluation in any monkey in the study.

Carcinogenesis

Two carcinogenicity bioassays were conducted in Fischer 344 rats. In the first study, male and female rats were given daily subcutaneous teriparatide injections of 5, 30, or 75 mcg/kg/day for 24 months from 2 months of age. These doses resulted in rat systemic exposures that were 3, 20, and 60 times higher than the systemic exposure observed in humans, respectively, following a subcutaneous dose of 20 mcg (based on AUC comparison). Teriparatide treatment resulted in a marked dose-related increase in the incidence of osteosarcoma, a rare malignant bone tumor, in both male and female rats. Osteosarcomas were observed at all doses and the incidence reached 40% to 50% in the high-dose groups. Teriparatide also caused a dose-related increase in osteoblastoma and osteoma in both sexes. No osteosarcomas, osteoblastomas or osteomas were observed in untreated control rats. The bone tumors in rats occurred in association with a large increase in bone mass and focal osteoblast hyperplasia. The second 2-year study was carried out in order to determine the effect of treatment duration and animal age on the development of bone tumors. Female rats were treated for different periods between 2 and 26 months of age with subcutaneous teriparatide doses of 5 and 30 mcg/kg (equivalent to 3 and 20 times the human exposure at the 20- mcg dose, respectively, based on AUC comparison). The study showed that the occurrence of osteosarcoma, osteoblastoma and osteoma was dependent upon dose and duration of teriparatide exposure. Bone tumors were observed when immature 2- month old rats were treated with 30 mcg/kg/day of teriparatide for 24 months or with 5 or 30 mcg/kg/day of teriparatide for 6 months. Bone tumors were also observed when mature 6-month old rats were treated with 30 mcg/kg/day of teriparatide for 6 or 20 months. Tumors were not detected when mature 6-month old rats were treated with 5 mcg/kg/day of teriparatide for 6 or 20 months. The results did not demonstrate a difference in susceptibility to bone tumor formation, associated with teriparatide treatment, between mature and immature rats.

No bone tumors were detected in a long-term monkey study.

Mutagenesis

Teriparatide was not genotoxic in any of the following test systems: the Ames test for bacterial mutagenesis; the mouse lymphoma assay for mammalian cell mutation; the chromosomal aberration assay in Chinese hamster ovary cells, with and without metabolic activation; and the in vivo micronucleus test in mice.

Impairment of Fertility

No effects on fertility were observed in male and female rats given subcutaneous teriparatide doses of 30, 100, or 300 mcg/kg/day prior to mating and in females continuing through gestation Day 6 (16 to 160 times the human dose of 20 mcg based on surface area, mcg/m).

Description

Teriparatide, a biosynthetic (rDNA origin) peptide fragment of the human parathyroid hormone (PTH), is a regulator of bone metabolism. It is produced by using a strain of Escherichia coli employing recombinant DNA technology. Its sequence is identical to that of 34 N-terminal amino acids (the biological active region) of the endogenous 84-amino acid human parathyroid hormone. It is a water-soluble protein with a molecular weight of 4117.8 daltons.

Pharmaceutical Particulars

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Shelf-life

Not more than 24 months.

Packaging Information

ZOTIDE is supplied in a cartridge containing 3 ml of clear colourless solution for injection.

USE ONLY WITH THE ZOTIDE DELIVERY DEVICE-PEN AND ZOTIDE PEN NEDDLES.

USE ZOTIDE CARTRIDGE UP TO 28 DAYS, INCLUDING THE FIRST INJECTION. AFTER 28 DAYS, THROW AWAY THE CARTRIDGE EVEN IF IT IS NOT COMPLETELY EMPTY.

Storage and Handling Instructions

ZOTIDE cartridge should be stored at 2–8ºC and should not be frozen.

Patient Counselling Information

What is ZOTIDE?

ZOTIDE contains a prescription medicine called teriparatide used to treat severe osteoporosis.

It is not known if teriparatide is safe and effective in children.

teriparatide should not be used in children and young adults whose bones are still growing.

Who should not Use ZOTIDE?

Do not use teriparatide if you are allergic to any of the ingredients in ZOTIDE.

Symptoms of a serious allergic reaction of teriparatide may include swelling of the face, lips, tongue or throat that may cause difficulty in breathing or swallowing. Call your healthcare provider right away or get emergency medical help if you get any of these symptoms.

What should I Tell My Healthcare Provider before Using Teriparatide?

Before you use teriparatide, tell your healthcare provider about all of your medical conditions, including if you:

  • have a certain bone disease called Paget's disease or other bone disease.
  • have bone cancer or have had a history of bone cancer.
  • are a young adult whose bones are still growing.
  • have had radiation therapy.
  • are affected with a condition that runs in your family that can increase your chance of getting cancer in your bones.
  • have or have had too much calcium in your blood (hypercalcemia).
  • have or have had a skin condition with painful sores or wounds caused by too much calcium.
  • have or have had kidney stones.
  • take medicines that contain digoxin.
  • are pregnant or plan to become pregnant. It is not known if teriparatide will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if teriparatide passes into your breastmilk. You should not breastfeed while taking teriparatide.

Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I Use ZOTIDE?

Read the detailed Instructions for Use included with your ZOTIDE delivery device.

Use ZOTIDE exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much ZOTIDE to use and when to use it.

Before you try to inject ZOTIDE yourself, a healthcare provider should teach you how to use the ZOTIDE delivery device to give your injection the right way.

Inject ZOTIDE 1 time each day in your thigh or abdomen (lower stomach area). Do not inject into a vein or a muscle. Talk to a healthcare provider about how to rotate injection sites.

The ZOTIDE delivery device has enough medicine for 28 days. 20- microgram dose of medicine should be injected each day. Do not inject all the medicine in the ZOTIDE delivery device at any one time. After the 28-day use period, discard the remaining medicine, even if it still contains some unused solution. Do not use ZOTIDE after the expiration date printed on the delivery device and packaging.

Do not transfer the medicine from the ZOTIDE delivery device to a syringe. This can result in taking the wrong dose of ZOTIDE. If you do not have pen needles to use with your ZOTIDE delivery device, talk with your healthcare provider. ZOTIDE should look clear and colorless. Do not use ZOTIDE if it has particles in it, or if it is cloudy or colored.

Inject ZOTIDE right away after you take the delivery device out of the refrigerator. After each use, safely remove the needle, recap the delivery device, and put it back in the refrigerator right away.

When you inject the first few doses of ZOTIDE, make sure you are in a place where you can sit or lie down right away in case you feel dizzy or have an abnormal heartbeat after the injection. Do not take more than 1 injection in the same day. Do not share your ZOTIDE delivery device with other people. If you take more ZOTIDE than prescribed, call your healthcare provider. If you take too much ZOTIDE, you may have nausea, vomiting, weakness, or dizziness. You should not use ZOTIDE for more than 2 years over your lifetime unless your healthcare provider finds that you need longer treatment because you have a high chance of breaking your bones. If your healthcare provider recommends calcium and vitamin D supplements, you can take them at the same time you take ZOTIDE.

Other Osteoporosis Treatment Modalities

Patients should be informed regarding the roles of supplemental calcium and/or vitamin D.

What are the Possible Side Effects of Teriparatide?

Teriparatide may cause serious side effects including:

Osteosarcoma

Patients should be made aware that in rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor). Although cases of osteosarcoma have been reported in patients using teriparatide no increased risk of osteosarcoma was observed in adult humans treated with teriparatide. There is little information about the chance of getting osteosarcoma in patients using teriparatide beyond 2 years.

Bone cancer (osteosarcoma): Tell your healthcare provider right away if you have pain in your bones, pain in any areas of your body that does not go away, or any new or unusual lumps or swelling under your skin that is tender to touch.

Hypercalcemia

Instruct patients taking teriparatide to contact a health care provider if they develop persistent symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy, muscle weakness).

Increased calcium in your blood. Tell your healthcare provider if you have nausea, vomiting, constipation, low energy, or muscle weakness. These may be signs there is too much calcium in your blood.

Orthostatic Hypotension

When initiating teriparatide treatment, instruct patients to be prepared to immediately sit or lie down during or after administration in case they feel lightheaded or have palpitations after the injection. Instruct patients to sit or lie down until the symptoms resolve. If symptoms persist or worsen, instruct patients to consult a healthcare provider before continuing treatment.

Decrease in blood pressure when you change positions. Some people may feel dizzy, get a fast heartbeat, or feel light-headed right after the first few doses of teriparatide. This usually happens within 4 hours of taking teriparatide and goes away within a few hours. For the first few doses, give your injections of teriparatide in a place where you can sit or lie down right away if you get these symptoms. If your symptoms get worse or do not go away, contact your healthcare provider before you continue using teripartide.

Worsening of your kidney stones. If you have or have had kidney stones your healthcare provider may check the calcium levels in your urine while you use teriparatide to see if there is worsening of this condition.

The most common side effects of teriparatide include:

  • pain
  • nausea
  • joint aches

These are not all the possible side effects of teriparatide. For more information, ask your

healthcare provider.

If you experience any side effects, talk to your doctor or pharmacist. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024.  

By reporting side effects, you can help provide more information on the safety of this product.

How should I Store ZOTIDE?

ZOTIDE cartridge should be stored at 2–8ºC and should not be frozen.

General information about the safe and effective use of teriparatide.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use teriparatide for a condition for which it was not prescribed.

Do not give teriparatide to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about ZOTIDE that is written for health professionals.

What are the Ingredients in ZOTIDE?

Active ingredient: teriparatide

Inactive ingredients: Glycerol IP, Succinic acid, Meta-cresol, Sodium hydroxide IP, and water for injection.

Details Of Manufacturer

Manufactured By:

Virchow Biotech Pvt Ltd,

Sy No 172 part, Gagillapur (V),

Dundigal-Gandimaisamma (M),

Medchal-Malkajgiri (D),

Telangana- 500043.

Registered Office:

Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg, Lower Parel,

Mumbai, Maharashtra, INDIA

Details of Permission or License Number with Date

02/RR/AP/2004/V/R dated 27/12/2004.

Date of Revision

06/12/2021