Arcalyst

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Infections

Interleukin -1 (IL-1) blockade may interfere with the immune response to infections. Treatment with another medication that works through inhibition of IL-1 has been associated with an increased risk of serious infections, and serious infections have been reported in patients taking ARCALYST [see Clinical Studies]. There was a greater incidence of infections in patients on ARCALYST (rilonacept) compared with placebo. In the controlled portion of the study, one infection was reported as severe, which was bronchitis in a patient on ARCALYST (rilonacept) .

In an open-label extension study, one patient developed bacterial meningitis and died [see ADVERSE REACTIONS]. ARCALYST (rilonacept) should be discontinued if a patient develops a serious infection. Treatment with ARCALYST (rilonacept) should not be initiated in patients with an active or chronic infection. In clinical studies, ARCALYST (rilonacept) has not been administered concomitantly with tumor necrosis factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of an IL-1 blocker in combination with TNF inhibitors. Taking ARCALYST (rilonacept) with TNF inhibitors is not recommended because this may increase the risk of serious infections.

Drugs that affect the immune system by blocking TNF have been associated with an increased risk of reactivation of latent tuberculosis (TB). It is possible that taking drugs such as ARCALYST (rilonacept) that block IL-1 increases the risk of TB or other atypical or opportunistic infections. Healthcare providers should follow current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before initiating therapy with ARCALYST (rilonacept) .

Immunosuppression

The impact of treatment with ARCALYST (rilonacept) on active and/or chronic infections and the development of malignancies is not known [see ADVERSE REACTIONS]. However, treatment with immunosuppressants, including ARCALYST (rilonacept) , may result in an increase in the risk of malignancies.

Immunizations

Since no data are available on either the efficacy of live vaccines or on the risks of secondary transmission of infection by live vaccines in patients receiving ARCALYST (rilonacept) , live vaccines should not be given concurrently with ARCALYST (rilonacept) . In addition, because ARCALYST (rilonacept) may interfere with normal immune response to new antigens, vaccinations may not be effective in patients receiving ARCALYST (rilonacept) . No data are available on the effectiveness of vaccination with inactivated (killed) antigens in patients receiving ARCALYST (rilonacept) .

Because IL-1 blockademay interfere with immune response to infections, it is recommended that prior to initiation of therapy with ARCALYST (rilonacept) adult and pediatric patients receive all recommended vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine. (See current Recommended Immunizations schedules at the website of the Centers for Disease Control. http://www.cdc.gov/vaccines/recs/schedules/).

Lipid Profile Changes

Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted [see ADVERSE REACTIONS].

Hypersensitivity

Hypersensitivity reactions associated with ARCALYST (rilonacept) administration in the clinical studies were rare. If a hypersensitivity reaction occurs, administration of ARCALYST (rilonacept) should be discontinued and appropriate therapy initiated.

Patient Counseling Information

See FDA-approved patient labeling.

The first injection of ARCALYST (rilonacept) should be performed under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer ARCALYST (rilonacept) , he/she should be instructed on aseptic reconstitution of the lyophilized product and injection technique. The ability to inject subcutaneously should be assessed to ensure proper administration of ARCALYST (rilonacept) , including rotation of injection sites. (See PATIENT INFORMATION Leaflet for ARCALYST™ (rilonacept) ). Arcalyst (rilonacept) should be reconstituted with preservative free Sterile Water for Injection to be provided by the pharmacy. A puncture-resistant container for disposal of vials, needles and syringes should be used. Patients or caregivers should be instructed in proper vial, syringe, and needle disposal, and should be cautioned against reuse of these items.

Injection-site Reactions: Physicians should explain to patients that almost half of the patients in the clinical trials experienced a reaction at the injection site. Injection-site reactions may include pain, erythema, swelling, pruritis, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles,warmth, and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or red. Any persistent reaction should be brought to the attention of the prescribing physician.

Infections: Patients should be cautioned that ARCALYST (rilonacept) has been associated with serious, life-threatening infections, and not to initiate treatment with ARCALYST (rilonacept) if they have a chronic or active infection. Patients should be counseled to contact their healthcare professional immediately if they develop an infection after starting ARCALYST (rilonacept) . Treatment with ARCALYST (rilonacept) should be discontinued if a patient develops a serious infection. Patients should be counseled not to take any IL-1 blocking drug, including ARCALYST (rilonacept) , if they are also taking a drug that blocks TNF such as etanercept, infliximab, or adalimumab. Use of ARCALYST (rilonacept) with other IL-1 blocking agents, such as anakinra, is not recommended.

Vaccinations: Prior to initiation of therapy with ARCALYST (rilonacept) physicians should review with adult and pediatric patients their vaccination history relative to current medical guidelines for vaccine use, including taking into account the potential of increased risk of infection during treatment with ARCALYST (rilonacept) .

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of rilonacept. The mutagenic potential of rilonacept was not evaluated.

Male and female fertility was evaluated in a mouse surrogate model using a murine analog of rilonacept. Male mice were treated beginning 8weeks prior to mating and continuing through female gestation day 15. Female mice were treated for 2weeks prior to mating and on gestation days 0, 3, and 6. The murine analog of rilonacept did not alter either male or female fertility parameters at doses up to 200 mg/kg (this dose is approximately 6-foldhigher than the 160mg maintenance dose based on body surface area).

Use In Specific Populations

Pregnancy

Pregnancy Category C. There are no adequate and well-controlled studies of ARCALYST (rilonacept) in pregnant women. Based on animal data, ARCALYST (rilonacept) may cause fetal harm. An embryo-fetal developmental toxicity study was performed in cynomolgus monkeys treated with 0, 5, 15 or 30 mg/kg given twice a week (highest dose is approximately 3.7-fold higher than the human doses of 160 mg based on body surface area.) The fetus of the only monkey with exposure to rilonacept during the later period of gestation showed multiple fusion and absence of the ribs and thoracic vertebral bodies and arches. Exposure to rilonacept during this time period was below that expected clinically. Likewise, in the cynomolgus monkey, all doses of rilonacept reduced serum levels of estradiol up to 64% compared to controls and increased the incidence of lumbar ribs compared to both control animals and historical control incidences. In perinatal and postnatal developmental toxicology studies in the mouse model using a murine analog of rilonacept (0, 20, 100 or 200 mg/kg), there was a 3-fold increase in the number of stillbirths in dams treated with 200 mg/kg three times per week (the highest dose is approximately 6-fold higher than the 160mg maintenance dose based on body surface area). ARCALYST (rilonacept) should be used during pregnancy only if the benefit justifies the potential risk to the fetus.

Nonteratogenic effects. A peri- and post-natal reproductive toxicology study was performed in which mice were subcutaneously administered a murine analogue of rilonacept at doses of 20, 100, 200 mg/kg three times per week (the highest dose is approximately 6-fold higher than the 160mg maintenance dose based on body surface area). Results indicated an increased incidence in unscheduled deaths of the F1offspring during maturation at all doses tested.

Nursing Mothers

It is not known whether rilonacept is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ARCALYST (rilonacept) is administered to a nursing woman.

Pediatric Use

Six pediatric patients with CAPS between the ages of 12 and 16 were treated with ARCALYST (rilonacept) at a weekly, subcutaneous dose of 2.2 mg/kg (up to a maximum of 160 mg) for 24-weeks during the open-label extension phase. These patients showed improvement from baseline in their symptom scores and in objective markers of inflammation (e.g. Serum Amyloid A and C-Reactive Protein).The adverse events included injection site reactions and upper respiratory symptoms as were commonly seen in the adult subjects. The trough drug levels for four pediatric patients measured at the end of the weekly dose interval (mean 20 mcg/mL, range 3.6 to 33 mcg/mL) were similar to those observed in adult patients with CAPS (mean 24 mcg/mL, range 7 to 56 mcg/mL).

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

When administered to pregnant primates, rilonacept treatment may have contributed to alterations in bone ossification in the fetus. It is not known if ARCALYST (rilonacept) will alter bone development in pediatric patients. Pediatric patients treated with ARCALYST (rilonacept) should undergo appropriate monitoring for growth and development. [see Use in Specific Populations]

Geriatric Use

In the placebo-controlled clinical studies in patients with CAPS and other indications, 70 patients randomized to treatment with ARCALYST (rilonacept) were ≥ 65 years of age, and 6 were ≥ 75 years of age. In the CAPS clinical trial, efficacy, safety and tolerability were generally similar in elderly patients as compared to younger adults; however, only ten patients ≥ 65 years old participated in the trial. In an open-label extension study of CAPS, a 71 year old woman developed bacterial meningitis and died [see ADVERSE REACTIONS]. Age did not appear to have a significant effect on steady state trough concentrations in the clinical study.

Patients with Renal Impairment

No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered subcutaneously in patients with renal impairment.

Patients with Hepatic Impairment

No formal studies have been conducted to examine the pharmacokinetics of rilonacept administered subcutaneously in patients with hepatic impairment.

Last reviewed on RxList: 8/6/2009
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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