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Secukinumab


General


Pronunciation

(sek ue KIN ue mab)


Brand Names: U.S.

  • Cosentyx
  • Cosentyx Sensoready Pen

Indications


Use: Labeled Indications

US labeling:

Ankylosing spondylitis: Treatment of active ankylosing spondylitis in adults.

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Psoriatic arthritis: Treatment of active psoriatic arthritis in adults.

Canadian labeling:

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.


Contraindications


Serious hypersensitivity reaction to secukinumab or any component of the formulation


Dosing and Administration


Dosing: Adult

Ankylosing spondylitis: SubQ:

With a loading dose: 150 mg at weeks 0, 1, 2, 3, and 4 followed by 150 mg every 4 weeks

Without a loading dose: 150 mg every 4 weeks

Plaque psoriasis: SubQ: 300 mg once weekly at weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Some patients may only require 150 mg per dose.

Psoriatic arthritis: SubQ:

With a loading dose: 150 mg at weeks 0, 1, 2, 3, and 4 followed by 150 mg every 4 weeks; consider an increase to 300 mg in patients who continue to have active psoriatic arthritis

Without a loading dose: 150 mg every 4 weeks; consider an increase to 300 mg in patients who continue to have active psoriatic arthritis

Coexistent moderate to severe plaque psoriasis: 300 mg once weekly at weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Some patients may only require 150 mg per dose.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturers labeling (has not been studied).


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling (has not been studied).


Reconstitution

Remove vial from the refrigerator and allow to stand for 15 to 30 minutes to reach room temperature. Reconstitute by slowly injecting 1 mL of sterile water onto the powder. Tilt the vial approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute; do not shake or invert. Let the vial sit at room temperature for 10 minutes to allow for dissolution (foaming may occur). Tilt the vial approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute again; do not shake or invert. Allow the vial to stand undisturbed at room temperature for approximately 5 minutes. The reconstituted solution should be essentially free of visible particles, clear to opalescent, and colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy, or discolored.

The Sensoready pen or prefilled syringe should be removed from the refrigerator and allowed to stand for 15 to 30 minutes to reach room temperature prior to administration.


Administration

SubQ: Allow to reach room temperature prior to injection. Inject into the front of thighs, lower abdomen ( ≥2 inches away from the navel) or outer upper arms; administer each injection at a different anatomic location than a previous injection and avoid areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis, or where there are scars or stretch marks. The Sensoready pen or prefilled syringe may be self-injected by the patient following proper training in SubQ injection technique; the lyophilized powder is to be administered by health care providers only.


Storage

Store intact vials, Sensoready pens, and prefilled syringes refrigerated at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Protect from light; keep in original carton. Do not freeze or shake. After reconstitution of the vial, use the solution immediately or store in the refrigerator at 2 ‚ ºC to 8 ‚ ºC (36 ‚ ºF to 46 ‚ ºF) for up to 24 hours. Do not freeze. The Sensoready pen or prefilled syringe may be stored at room temperature for up to an hour immediately prior to administration. Discard any unused portion.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous [preservative free]:

Cosentyx Sensoready Pen: 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Cosentyx: 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80]


Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination


Monitoring Parameters

Signs and symptoms of infection, active tuberculosis (during and after treatment), and signs/symptoms of inflammatory bowel disease


Adverse Reactions


Frequency not always defined.

Central nervous system: Headache ( ≥2%)

Dermatologic: Urticaria ( ≤1%), candidiasis

Endocrine & metabolic: Hypercholesterolemia ( ≥2%)

Gastrointestinal: Diarrhea (3% to 4%), nausea ( ≥2%), mucocutaneous candidiasis (1%), inflammatory bowel disease ( ≤1%), oral herpes ( ≤1%), exacerbation of inflammatory bowel disease

Hypersensitivity: Anaphylaxis, hypersensitivity

Infection: Infection (29% to 48%), serious infection ( ≤1%), herpes virus infection, staphylococcal infection

Respiratory: Nasopharyngitis (11% to 12%), upper respiratory tract infection (3%), pharyngitis (1%), rhinitis (1%), rhinorrhea ( ≤1%)

<1% (Limited to important or life-threatening): Conjunctivitis, Crohn disease, exacerbation of Crohn disease, exacerbation of ulcerative colitis, immunogenicity, impetigo, increased serum transaminases, neutropenia, oral candidiasis, otitis externa, otitis media, sinusitis, tinea pedis, tonsillitis, ulcerative colitis


Warnings/Precautions


Concerns related to adverse effects:

- Hypersensitivity reactions: Urticaria and anaphylaxis have been reported; discontinue immediately if signs/symptoms of a serious hypersensitivity reaction develop and initiate appropriate treatment.

- Infections: Secukinumab may increase the risk of infections. A higher rate of infections was observed with secukinumab treatment in clinical trials, including nasopharyngitis, upper respiratory tract infection, and mucocutaneous candida infection; the incidence of some types of infection appeared to be dose-dependent. Use with caution in patients with a chronic infection or a history of recurrent infection. In patients who develop a serious infection, monitor closely and discontinue use until the infection resolves.

- Tuberculosis: Patients should be evaluated for tuberculosis infection prior to initiating therapy; do not initiate therapy in patients with an active tuberculosis infection. Consider antituberculosis therapy if an adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis. Monitor all patients for signs and symptoms of active tuberculosis during and after treatment.

Disease related concerns:

- Inflammatory bowel disease: Treatment with secukinumab may cause exacerbations (some serious) and new onset of inflammatory bowel of inflammatory bowel disease; monitor patients for signs and symptoms of inflammatory bowel disease.

Dosage form specific issues:

- Latex: Some dosage forms may contain dry natural rubber (latex).

Other warnings/precautions:

- Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; non-live vaccines administered during secukinumab therapy may not elicit an immune response sufficient to prevent disease.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. In general, maternal use of monoclonal antibodies during pregnancy may increase the risk of infection to the exposed infant or interfere with vaccine administration in the newborn (Mervic 2014). Other agents are currently preferred for the treatment of plaque psoriasis in pregnant women (Hsu 2012).


Actions


Pharmacology

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.


Distribution

Vd: 7.1 to 8.6 L


Metabolism

Expected to be degraded into small peptides and amino acids via catabolic pathways similar to that which is seen with endogenous IgG


Time to Peak

~6 days


Half-Life Elimination

22 to 31 days


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience signs of common cold, rhinitis, pharyngitis, or diarrhea. Have patient report immediately to prescriber signs of infection, severe dizziness, or passing out (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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