Questions about Rheumatoid Arthritis? Get answers from our expert.

Anakinra (Systemic)


VA CLASSIFICATION
Primary: MS109

Commonly used brand name(s): Kineret.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antirheumatic—

Biological response modifier—

Indications

Accepted

Arthritis, rheumatoid (treatment)— Anakinra is indicated for the reduction in signs and symptoms of moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed one or more disease modifying antirheumatic drugs (DMARDs). Anakinra can be used alone or in combination with DMARDs such as azothiaprine, gold, hydrochloroquine, leflunomide, methotrexate, and sulfasalazine. It should not be used with other tumor necrosis factor (TNF) blocking agents. {02}{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Anakinra is produced by recombinant DNA technology using an E. coli bacterial expression system {01}
Molecular weight—
    17.3 kilodaltons{01}


pH
    pH of prepared solution is 6.5{01}

Mechanism of action/Effect:

Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. {01}

IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. IL-1 has a broad range of activities including cartilage degradation by its induction of the rapid loss of proteoglycans, as well as stimulation of bone resorption. The levels of the naturally occurring interleukin-1 receptor antagonist (IL-1Ra) in synovium and synovial fluid from rheumatoid arthritis patients are not sufficient to compete with the elevated amount of locally produced IL-1. {01}

Absorption:

The absolute bioavailability of anakinra after a 70 mg subcutaneous bolus injection in healthy subjects is 95%. {01}

Half-life:
Terminal—

   • Subcutaneous administration— 4 to 6 hours {01}

Time to peak concentration:

Subcutaneous administration— 3 to 7 hours {01}

Renal impairment
    The mean plasma clearance of anakinra decreased 70 to 75% in normal subjects with severe or end stage renal disease.{01}


Precautions to Consider

Carcinogenicity

Studies in animals have not been done to evaluate the carcinogenic potential of anakinra. {01}

Mutagenicity

In studies using a standard in vivo and in vitro battery of mutagenesis assays, anakinra did not induce gene mutations in either bacteria or mammalian cells. {01}

Pregnancy/Reproduction
Fertility—
Anakinra had no adverse effects on male or female fertility in rats and rabbits at doses of up to 100-fold greater than the human dose. {01}

Pregnancy—
Adequate and well-controlled studies have not been done in humans. {01}

Reproductive studies conducted with anakinra on rats and rabbits at doses up to 100 times the human dose have revealed no evidence of harm to the fetus. {01}

FDA Pregnancy Category B {01}

Breast-feeding

It is not known whether anakinra is distributed into human breast milk. {01}

Pediatrics

No information is available on the relationship of age to the effects of anakinra in the pediatric population.{01} Safety and efficacy have not been established. {01}


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of anakinra in the elderly. {01}

However, greater sensitivity of some older individuals cannot be ruled out. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly. Anakinra is substantially excreted by the kidney. The risk of toxic reactions may be greater in patients with renal impairment. {01}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

» Vaccines, live virus    (no data are available on the effects of vaccination with live viruses {02}or secondary transmission of infection by live vaccines in patients receiving anakinra therapy; concurrent use of live-virus vaccines {02}is not recommended. Vaccination may not be effective in patients receiving anakinra.{01})


» Vaccines, inactivated virus or bacterial antigens    (no data are available on the effects of vaccination with inactivated virus or bacterial antigens; vaccinations may not be effective if you are taking anakinra {02})


» Etanercept    (when used concurrently, there is a higher incidence of serious infections{01})


» Tumor necrosis factor (TNF) blocking agents,     (other TNF blocking agents should only be used with extreme caution when no satisfactory alternatives exist{01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Neutrophil count {01}    (may be decreased{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to anakinra or any of its components or{01}
» Hypersensitivity to E.coli-derived proteins{01}
» Infections, active    (anakinra may potentially suppress normal defense mechanisms against infections. {01})

    (anakinra therapy should not be initiated in patients with active infections; if a patient develops a serious infection while receiving anakinra, continued {03}use of anakinra should be evaluated by the physician{03}; the safety and efficacy of anakinra in patients with a history of certain{03} chronic infections have not been evaluated )


Risk-benefit should be considered when the following medical problems exist
» Immunosuppression{01}    (safety and efficacy of anakinra in immunosuppressed patients have not been evaluated{01})


» Severe or end stage renal disease{01}    (mean plasma clearance of anakinra decreased 70 to 75% in normal subjects with severe or end stage renal disease;{01} renal status should be assessed periodically throughout therapy{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Neutrophil count    (should be assessed prior to initiating anakinra treatment, and monthly for the first {03}three months while receiving anakinra, and quarterly thereafter for a period up to one year. {01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Infections such as bone and joint infection {01}(pain in the bone or joint; swelling; tenderness or warmth on skin; fever), cellulitis {01}(itching; pain; redness; swelling; tenderness or warmth on skin), and pneumonia {01}(chest pain; cough; fever or chills; sneezing; shortness of breath; sore throat; troubled breathing; tightness in chest; wheezing)
    
influenza-like symptoms {01}(chills; cough; diarrhea; fever; general feeling of discomfort or illness; headache; joint pain; loss of appetite; muscle aches and pains; nausea; runny nose; shivering; sore throat; sweating; trouble sleeping; unusual tiredness or weakness; vomiting)
    
injection site reaction {01}(redness or purple discoloration of skin; inflammation; pain)
    
sinusitis {01}(pain or tenderness around eyes and cheekbones; fever; stuffy or runny nose; headache; cough; shortness of breath or troubled breathing; tightness of chest or wheezing)
    
upper respiratory tract infection {01}(cough; fever; sneezing or sore throat )
Note: Note: Patients with asthma may have a higher risk of developing serious infections.{01}



Incidence rare
    
Hypersensitivity reactions {01}(itching; rash; hives; swelling of face or lips; tightness in chest; wheezing or troubled breathing)
    
neutropenia {01}( black, sticky stools; chills; cough; fever; lower back or side pain; painful or difficult urination; pale skin; shortness of breath; sore throat; ulcers, sores, or white spots in mouth; unusual bleeding or bruising; unusual tiredness or weakness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Diarrhea {01}
    
headache {01}
    
nausea {01}
    
pain, abdominal {01}
{01}




Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Note: No serious toxicities attributed to anakinra were seen in sepsis trials when administered at doses up to 35 times those given to patients with rheumatoid arthritis over a 72-hour treatment period. {01}


Treatment of overdose


Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Anakinra (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to anakinra or any of its components

Hypersensitivity to E.coli-derived products.
Other medications, especially vaccines (live virus) or tumor necrosis factor blocking agents (TNF).
Other medical problems, especially infections (active), immunosuppression, and severe or end stage renal disease.

Proper use of this medication
» Reading patient directions carefully with regard to:

   • Safe handling and disposal of needles and syringes
   • Proper injection technique
   • Stability of the injection


» Proper dosing
Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses.

Proper storage

Precautions while using this medication
» Importance of close monitoring by physician, especially for infections

» Telling physician right away if signs or symptoms of infections such as bone and joint infection (pain in the bone or joint, swelling, fever), cellulitis (itching, pain, redness, swelling or tenderness on skin), and pneumonia (chest pain, fever or chills, cough or hoarseness) occur

» Avoiding immunizations unless approved by physician


Side/adverse effects
Signs of potential side effects, especially infections, influenza-like symptoms, injection site reaction, sinusitis, upper respiratory infection, hypersensitivity reactions, or neutropenia.


Parenteral Dosage Forms

ANAKINRA INJECTION

Usual Adult Dose
Arthritis, rheumatoid
Subcutaneous, 100 mg per day {01}


Usual adult prescribing limits
100 mg per day {01}

Usual Pediatric Dose
Safety and efficacy have not been established. {01}

Usual Geriatric Dose
See Usual adult dose

Usual geriatric prescribing limits
See Usual adult prescribing limits

Strength(s) usually available
U.S.—


100 mg (Rx) [Kineret{01} ( sodium citrate 1.29 mg ) (sodium chloride 5.48 mg ) (disodium EDTA 0.12 mg ) ( polysorbate 80 (0.70 mg)) (water for injection, USP)]

Canada—


100 mg (Rx) [Kineret]{04}

Note: Anakinra is supplied in single-use , preservative free, glass prefilled syringes with 27 gauge needles. Anakinra is dispensed in packs containing 7 or 28 syringes. {01}


Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF). {01}Protect from freezing. Protect from light.{01}

Stability:
Because the single-dose injection contains no preservative, each syringe should be used to administer one dose only. Any unused portion of the solution must be discarded. Do not save unused drug for later administration.{01}

Auxiliary labeling:
   • Do not shake.
   • Do not freeze.



Developed: 04/08/2002
Revised: 06/17/2002



References
  1. Product Information: Kineret™, anakinra. Amgen, Thousand Oaks, CA, (PI issued 11/14/2001) reviewed 2/2002.
  1. Expert committee comments, 5/2002.
  1. Manufacturer's comments, 5/2002.
  1. Drug Product Database Online, Canada, 6/2002
Hide
(web3)