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Drug overview for TEGSEDI (inotersen sodium):
Generic name: inotersen sodium (IN-oh-TER-sen)
Drug class: Amyloidosis Agents - Transthyretin (TTR) Suppression
Therapeutic class: Endocrine
Inotersen sodium, an antisense oligonucleotide that targets transthyretin (TTR) messenger RNA (mRNA), is a TTR silencer.
No enhanced Uses information available for this drug.
Generic name: inotersen sodium (IN-oh-TER-sen)
Drug class: Amyloidosis Agents - Transthyretin (TTR) Suppression
Therapeutic class: Endocrine
Inotersen sodium, an antisense oligonucleotide that targets transthyretin (TTR) messenger RNA (mRNA), is a TTR silencer.
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for TEGSEDI (inotersen sodium) have been approved by the FDA:
Indications:
Transthyretin familial amyloid polyneuropathy
Professional Synonyms:
Polyneuropathy due to ATTR
Polyneuropathy due to transthyretin amyloidosis
Transthyretin amyloid polyneuropathy
TTR familial amyloid polyneuropathy
Indications:
Transthyretin familial amyloid polyneuropathy
Professional Synonyms:
Polyneuropathy due to ATTR
Polyneuropathy due to transthyretin amyloidosis
Transthyretin amyloid polyneuropathy
TTR familial amyloid polyneuropathy
The following dosing information is available for TEGSEDI (inotersen sodium):
Dosage of inotersen sodium is expressed in terms of inotersen.
Inotersen is administered by subcutaneous injection only. The injection is administered once weekly (preferably on the same day each week for consistency of dosing). Inotersen sodium injection is commercially available in single-use prefilled syringes.
The prefilled syringes should be stored at 2-8degreesC in the original carton and protected from light until time of use; the drug should not be frozen. If necessary, the prefilled syringes may be stored at room temperature (up to 30degreesC) in the original container for up to 6 weeks; the drug should be discarded if it is not used within this time period. Exposure of inotersen to temperatures above 30degreesC should be avoided.
Inotersen may be self-administered after the patient and/or their caregiver have received appropriate training. The first self-administered injection should be performed under the guidance of an appropriately qualified healthcare professional. Prior to administration, the prefilled syringe should be allowed to reach room temperature for at least 30 minutes; other warming methods (e.g., microwave, hot water, placement near other heat sources) should not be used.
The needle cap should not be removed from the syringe until immediately prior to injection. The solution should be inspected visually prior to administration, and should not be used if any cloudiness, particulate matter, or discoloration is present. Subcutaneous injections of inotersen should be made into the abdomen (except within 2 inches of the navel), upper thigh, or outer area of the upper arm (by a caregiver).
Injection sites should be rotated. Injections should not be made into the waistline or other areas where pressure or rubbing from clothing may occur; injections into areas where the skin is tender, bruised, red, damaged, tattooed, or scarred also should be avoided.
The prefilled syringes should be stored at 2-8degreesC in the original carton and protected from light until time of use; the drug should not be frozen. If necessary, the prefilled syringes may be stored at room temperature (up to 30degreesC) in the original container for up to 6 weeks; the drug should be discarded if it is not used within this time period. Exposure of inotersen to temperatures above 30degreesC should be avoided.
Inotersen may be self-administered after the patient and/or their caregiver have received appropriate training. The first self-administered injection should be performed under the guidance of an appropriately qualified healthcare professional. Prior to administration, the prefilled syringe should be allowed to reach room temperature for at least 30 minutes; other warming methods (e.g., microwave, hot water, placement near other heat sources) should not be used.
The needle cap should not be removed from the syringe until immediately prior to injection. The solution should be inspected visually prior to administration, and should not be used if any cloudiness, particulate matter, or discoloration is present. Subcutaneous injections of inotersen should be made into the abdomen (except within 2 inches of the navel), upper thigh, or outer area of the upper arm (by a caregiver).
Injection sites should be rotated. Injections should not be made into the waistline or other areas where pressure or rubbing from clothing may occur; injections into areas where the skin is tender, bruised, red, damaged, tattooed, or scarred also should be avoided.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for TEGSEDI (inotersen sodium):
There are 0 contraindications.
There are 4 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Selected Nephrotoxic Agents/Inotersen SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inotersen can cause glomerulonephritis and renal toxicity. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) CLINICAL EFFECTS: Concurrent use of inotersen with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: Patients with pre-existing renal impairment. PATIENT MANAGEMENT: The US manufacturer of inotersen state that caution should be used when administered concurrently with potentially nephrotoxic agents or agents that impair renal function.(1) If concurrent therapy is warranted, monitor renal function closely.(1) DISCUSSION: The safety of inotersen has not been studied in patients receiving other known potentially nephrotoxic agents. Inotersen is only available through a Tegsedi REMS program because of the risk of glomerulonephritis and severe thrombocytopenia.(1) |
ABELCET, ACYCLOVIR, ACYCLOVIR SODIUM, ACYCLOVIR SODIUM-0.9% NACL, ADEFOVIR DIPIVOXIL, AFINITOR, AFINITOR DISPERZ, AMBISOME, AMIKACIN SULFATE, AMPHOTERICIN B, AMPHOTERICIN B LIPOSOME, ASTAGRAF XL, BIKTARVY, CIMDUO, CISPLATIN, COMPLERA, CYCLOSPORINE, CYCLOSPORINE MODIFIED, DELSTRIGO, DESCOVY, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EMTRICITABINE-TENOFOVIR DISOP, ENVARSUS XR, EVEROLIMUS, FYARRO, GENGRAF, GENTAMICIN SULFATE, GENTAMICIN SULFATE IN NS, GENVOYA, HEPSERA, KANAMYCIN SULFATE, KEMOPLAT, LUPKYNIS, METHOTREXATE, METHOTREXATE SODIUM, NEOMYCIN SULFATE, NEORAL, ODEFSEY, PENTAM 300, PENTAMIDINE ISETHIONATE, PROGRAF, SANDIMMUNE, SIROLIMUS, STREPTOMYCIN SULFATE, STRIBILD, SYMFI, SYMFI LO, SYMTUZA, TACROLIMUS, TACROLIMUS XL, TEMSIROLIMUS, TENOFOVIR DISOPROXIL FUMARATE, TOBRAMYCIN, TOBRAMYCIN SULFATE, TORISEL, TORPENZ, TRUVADA, VALACYCLOVIR, VALACYCLOVIR HCL, VALTREX, VANCOMYCIN, VANCOMYCIN HCL, VANCOMYCIN HCL-0.9% NACL, VANCOMYCIN HCL-D5W, VEMLIDY, VIREAD, ZORTRESS, ZOVIRAX |
| Inotersen/Anticoagulants; Antiplatelets SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inotersen causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia.(1) CLINICAL EFFECTS: Concurrent use of inotersen with anticoagulants and/or antiplatelet agents may result in additive or synergistic effects, including fatal and non-fatal intracranial hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may also be greater in patients greater than 60 years or have a prior history of major bleeding events. Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Inotersen should be administered with caution in patients receiving anticoagulants and/or antiplatelet agents.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Monitor platelet count frequently. If platelet count is less than 50, stop inotersen treatment and consider discontinuation of any anticoagulant and/or antiplatelet agents. Monitor for signs and symptoms of thrombocytopenia; such as, unusual or prolonged bleeding (petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. DISCUSSION: In a clinical study, platelet counts below 100 occurred in 25% of inotersen-treated patients, compared with 2% of patients on placebo. Platelet counts below 75 occurred in 14% of inotersen-treated patients, compared to no patients on placebo. In study 1 and its extension study, 39% of inotersen-treated patients with a baseline platelet count below 200 had a nadir platelet count below 75, compared to 6% of patients with baseline platelet counts 200 or higher. Three inotersen-treated patients (3%) had sudden severe thrombocytopenia (platelet count below 25). One patient experienced a fatal intracranial hemorrhage.(1) Inotersen is only available through a Tegsedi REMS program because of the risk of severe thrombocytopenia and the risk of glomerulonephritis.(1) |
AA 6%-D10W-CALCIUM-HEPARIN, ACETYL SALICYLIC ACID, AGGRASTAT, ANISINDIONE, ARGATROBAN, ARGATROBAN-0.9% NACL, ARIXTRA, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN, ASPIRIN-DIPYRIDAMOLE ER, BRILINTA, BUTALBITAL-ASPIRIN-CAFFEINE, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, CILOSTAZOL, CLOPIDOGREL, CLOPIDOGREL BISULFATE, DABIGATRAN ETEXILATE, DICUMAROL, DIPYRIDAMOLE, DURLAZA, EFFIENT, ELIQUIS, ELMIRON, ENOXAPARIN SODIUM, ENOXILUV, EPTIFIBATIDE, FONDAPARINUX SODIUM, FRAGMIN, HEPARIN LOCK, HEPARIN SODIUM, HEPARIN SODIUM IN 0.45% NACL, HEPARIN SODIUM-0.45% NACL, HEPARIN SODIUM-0.9% NACL, HEPARIN SODIUM-D5W, JANTOVEN, KENGREAL, LOVENOX, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, PENTOSAN POLYSULFATE SODIUM, PLAVIX, PRADAXA, PRASUGREL HCL, RIVAROXABAN, SAVAYSA, TICAGRELOR, TIROFIBAN HCL, WARFARIN SODIUM, XARELTO, YOSPRALA, ZONTIVITY |
| Inotersen/Non-Steroidal Anti-Inflammatory Drugs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inotersen causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia. Inotersen can also cause glomerulonephritis and renal toxicity. NSAIDs can impair thromboxane-dependent platelet aggregation by blocking the formation of thromboxane A2. Concurrent administration with NSAIDs may also result in additive or synergistic effects on renal function.(1) CLINICAL EFFECTS: Concurrent use of inotersen with NSAIDs may result in additive or synergistic effects, including fatal and non-fatal intracranial hemorrhage, or renal toxicity.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may also be greater in patients greater than 60 years or have a prior history of major bleeding events. Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding. Patients with pre-existing renal impairment. PATIENT MANAGEMENT: Inotersen should be administered with caution in patients receiving NSAIDs. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Monitor platelet count frequently. If platelet count is less than 50, stop inotersen treatment and consider discontinuation of NSAID. Monitor for signs and symptoms of thrombocytopenia; such as, unusual or prolonged bleeding (petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. Monitor renal function closely. DISCUSSION: In a clinical study, platelet counts below 100 occurred in 25% of inotersen-treated patients, compared with 2% of patients on placebo. Platelet counts below 75 occurred in 14% of inotersen-treated patients, compared to no patients on placebo. In study 1 and its extension study, 39% of inotersen-treated patients with a baseline platelet count below 200 had a nadir platelet count below 75, compared to 6% of patients with baseline platelet counts 200 or higher. Three inotersen-treated patients (3%) had sudden severe thrombocytopenia (platelet count below 25). One patient experienced a fatal intracranial hemorrhage.(1) The safety of inotersen has not been studied in patients receiving other known potentially nephrotoxic agents.(1) Inotersen is only available through a Tegsedi REMS program because of the risk of severe thrombocytopenia and the risk of glomerulonephritis.(1) |
ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, BROMFENAC SODIUM, BUPIVACAINE-KETOROLAC-KETAMINE, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, DIFLUNISAL, DOLOBID, EC-NAPROSYN, ELYXYB, ETODOLAC, ETODOLAC ER, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, LOFENA, LURBIPR, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, OXAPROZIN, PHENYLBUTAZONE, PIROXICAM, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RELAFEN DS, ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SPRIX, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TOLECTIN 600, TOLMETIN SODIUM, TORONOVA II SUIK, TORONOVA SUIK, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VIMOVO, VIVLODEX, ZIPSOR, ZORVOLEX, ZYNRELEF |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
There are 0 moderate interactions.
The following contraindication information is available for TEGSEDI (inotersen sodium):
Drug contraindication overview.
*Platelet counts <100,000/mm3. *History of acute glomerulonephritis attributed to inotersen. *History of hypersensitivity to inotersen or any ingredient in formulation.
*Platelet counts <100,000/mm3. *History of acute glomerulonephritis attributed to inotersen. *History of hypersensitivity to inotersen or any ingredient in formulation.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Liver transplant rejection |
There are 2 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Glomerulonephritis |
| Thrombocytopenic disorder |
There are 0 moderate contraindications.
The following adverse reaction information is available for TEGSEDI (inotersen sodium):
Adverse reaction overview.
Adverse effects reported in >=20% of patients receiving inotersen and more frequently than with placebo in clinical studies include injection site reactions, nausea, headache, fatigue, thrombocytopenia, and fever.
Adverse effects reported in >=20% of patients receiving inotersen and more frequently than with placebo in clinical studies include injection site reactions, nausea, headache, fatigue, thrombocytopenia, and fever.
There are 21 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hyperbilirubinemia Thrombocytopenic disorder |
Abnormal hepatic function tests Anemia Bacterial infection Cardiac arrhythmia Chorea Eosinophilia Glomerulonephritis Hypersensitivity drug reaction Hypertension Increased alanine transaminase Increased aspartate transaminase Kidney disease with reduction in glomerular filtration rate (GFr) Nephrotic syndrome Orthostatic hypotension |
| Rare/Very Rare |
|---|
|
ANCa-positive vasculitis Cerebrovascular accident Cervicocephalic arterial dissection Clostridioides difficile infection Paraplegia |
There are 24 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Fatigue Fever Headache disorder Injection site sequelae Nausea Vitamin A deficiency |
Anorexia Arthralgia Bruising Cachexia Chest pain Chills Dysphagia Dyspnea Flu-like symptoms Flushing Myalgia Palmar rash Paresthesia Peripheral edema Syncope Vomiting Xerostomia |
| Rare/Very Rare |
|---|
|
Gait abnormality |
The following precautions are available for TEGSEDI (inotersen sodium):
Safety and efficacy of inotersen have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
There are no available data on the developmental risks associated with the use of inotersen in pregnant women. Administration of high doses of inotersen to pregnant rabbits every other day during the period of organogenesis resulted in premature births and reduced fetal body weights at doses associated with maternal toxicity. No adverse developmental effects or effects on fertility were noted when inotersen (or a rodent-specific pharmacologically active surrogate) was administered every other day to male and female mice prior to and during mating and continuing in female mice throughout the period of organogenesis.
A pregnancy registry has been established; encourage patients to enroll by calling 1-877-465-7510, emailing tegsedipregnancy@ubc.com or visiting www.tegsedipregnancystudy.com.
A pregnancy registry has been established; encourage patients to enroll by calling 1-877-465-7510, emailing tegsedipregnancy@ubc.com or visiting www.tegsedipregnancystudy.com.
It is not known whether inotersen is distributed into human milk; the drug has been detected in the milk of lactating mice. The effects of inotersen on the breast-fed infant or on milk production are not known. Consider the benefits of breast-feeding and the woman's clinical need for inotersen along with any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
In clinical trials of inotersen, 45% of patients were >=65 years of age. Although no overall differences in efficacy or pharmacokinetics have been observed between geriatric patients and younger adults, the risk of certain adverse effects (e.g., heart failure, chills, myalgia, extremity pain) may be increased in patients >=65 years of age.
The following prioritized warning is available for TEGSEDI (inotersen sodium):
WARNING: This medication decreases the number of platelets in your blood, which may cause serious (even fatal) bleeding problems. Tell your doctor right away if you notice symptoms such as easy bruising, a rash of tiny reddish-purple spots (especially on your lower legs), bleeding gums, nosebleeds, blood in urine/stools, vomiting or coughing up blood, neck stiffness, unusual severe headache, or unusual/heavy menstrual periods (women). This medication can cause serious kidney damage that may result in the need for dialysis.
Tell your doctor right away if you have swelling in your face/feet/hands, shortness of breath, cough, blood in urine, brown/foamy urine, or change in amount of urine. Careful monitoring and treatment by your doctor may decrease your risk for serious side effects. Lab and/or medical tests (such as kidney/liver function, complete blood count, urine tests) should be done before you start using this medication, while you are using it, and for 8 weeks after stopping treatment.
Keep all medical and lab appointments. To receive inotersen in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.
WARNING: This medication decreases the number of platelets in your blood, which may cause serious (even fatal) bleeding problems. Tell your doctor right away if you notice symptoms such as easy bruising, a rash of tiny reddish-purple spots (especially on your lower legs), bleeding gums, nosebleeds, blood in urine/stools, vomiting or coughing up blood, neck stiffness, unusual severe headache, or unusual/heavy menstrual periods (women). This medication can cause serious kidney damage that may result in the need for dialysis.
Tell your doctor right away if you have swelling in your face/feet/hands, shortness of breath, cough, blood in urine, brown/foamy urine, or change in amount of urine. Careful monitoring and treatment by your doctor may decrease your risk for serious side effects. Lab and/or medical tests (such as kidney/liver function, complete blood count, urine tests) should be done before you start using this medication, while you are using it, and for 8 weeks after stopping treatment.
Keep all medical and lab appointments. To receive inotersen in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.
The following icd codes are available for TEGSEDI (inotersen sodium)'s list of indications:
| Transthyretin familial amyloid polyneuropathy | |
| E85.1 | Neuropathic heredofamilial amyloidosis |
| G63 | Polyneuropathy in diseases classified elsewhere |
Formulary Reference Tool