Learn more about AbbVie's response to COVID-19

Moderate to Severe

Juvenile Idiopathic Arthritis

Non-Infectious

Intermediate, Posterior and Panuveitis

Active

Psoriatic Arthritis

Moderate to Severe

Hidradenitis Suppurativa

Refractory, Moderate to Severe

Atopic Dermatitis

Gastroenterology

Moderate to Severe

Crohn's Disease

Moderate to Severe

Pediatric Crohn's Disease

Moderate to Severe

Ulcerative Colitis

Moderate to Severe

Pediatric Ulcerative Colitis

Ophthalmology

Non-Infectious

Intermediate, Posterior and Panuveitis

For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients1
For active psoriatic arthritis (PsA) in adult TNFi-IR patients1

SAFETY DATA
FROM 8 TRIALS
ACROSS 2 RHEUMATOLOGY INDICATIONS1-3,a

>6200
patients evaluated
upadacitinibb

>6200
patients evaluated
upadacitinibb

>8200
patient-years
exposure to RINVOQ 15 mg
as of 6/30/2020c

~4.5years
maximum exposure in RA (~2.6 years median),
~3 years maximum exposure in PsA
(~1.3 years median)
to RINVOQ 15 mg
as of 6/30/2020

~4.5years
maximum exposure
in RA (~2.6 years median),
~3 years maximum exposure in PsA
(~1.3 years median)
to RINVOQ 15 mg
as of 6/30/2020

Clinical Trial Overview

SELECT-PsA 1 Study Design Intro:1
24-week, double-blind, active placebo and comparator‑controlled study of 1705 adult patients with moderate to severe PsA who had an inadequate response or intolerance to at least one non‑biologic DMARD. Patients were randomized to receive either upadacitinib, active comparator, or placebo. The primary endpoint was proportion of patients achieving ACR20 response at Week 12 vs placebo.

SELECT-PsA 2 Study Design Intro:1
24-week, double-blind, placebo-controlled study of 642 adult patients with moderate to severe active PsA who had an inadequate response or intolerance to at least one biologic DMARD. Patients were randomized to receive upadacitinib or placebo. The primary endpoint was proportion of patients achieving ACR20 response at Week 12 vs placebo.

SELECT‑EARLY (Study RA‑I) Study
Design Intro:
1,6
48‑week, double‑blind, active comparator‑controlled study of 947 adult patients with moderate to severe RA who were MTX‑naïve. Patients were randomized to receive RINVOQ 15 mg once daily (n=317) or MTX (n=314). The primary endpoint was ACR50 response at Week 12. At Week 26, non‑responding patients were rescued according to prespecified criteria.

SELECT‑MONOTHERAPY (Study RA‑II) Study Design Intro:1,7
14‑week, double‑blind, active comparator‑controlled study of 648 adult patients with moderate to severe RA who had an inadequate response to MTX. Patients were randomized to receive RINVOQ 15 mg once daily (n=217) or cMTX weekly (n=216). The primary endpoint was ACR20 response at Week 14.

SELECT-NEXT (Study RA-III) Study Design Intro:1,8
12-week, double-blind, placebo-controlled study of 661 adult patients with moderate to severe RA who had an inadequate response to csDMARDs. Patients on background csDMARDs were randomized to receive RINVOQ 15 mg once daily (n=221) or placebo (n=221). The primary endpoint was ACR20 response at Week 12.

SELECT-COMPARE (Study RA-IV) Study Design Intro:1,9
48-week, double-blind, active comparator-controlled study of 1629 adult patients with moderate to severe RA who had an inadequate response to MTX. Patients on background MTX were randomized to receive RINVOQ 15 mg once daily (n=651), placebo (n=651), or active comparator (n=327). The primary endpoint was ACR20 response at Week 12 vs placebo. Prespecified blinded rescue protocols occurred at Weeks 14, 18, 22, or 26.

SELECT-BEYOND (Study RA-V) Study Design Intro:1,10
12-week, double-blind, placebo-controlled study of 499 adult patients with moderate to severe RA who have had an inadequate response or intolerance to biological DMARDs. Patients on background csDMARDs were randomized to receive RINVOQ 15 mg once daily (n=164) or placebo (n=169). The primary endpoint was ACR20 response at Week 12.

SELECT‑CHOICE Study Design Intro:11
24‑week, double‑blind, active comparator‑controlled study of 612 adult patients with moderate to severe RA who had an inadequate response or intolerance to bDMARDs. Patients on stable csDMARDs were randomized to receive RINVOQ 15 mg once daily (n=303) or active comparator at 0, 2, and 4 weeks, and every 4 weeks thereafter (n=309). The primary endpoint was ▵DAS28‑CRP (noninferiority) at Week 12.

WELL-STUDIED
Safety Profile in PsA1
Safety data at Week 24

Adverse Events of Special Interest3,4,12,13

Safety data in PsA

VACCINATION:
Use of live, attenuated vaccines during, or immediately prior to, RINVOQ therapy is not recommended. Prior to initiating RINVOQ, patients should be brought up to date on all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.

TEAEs were defined as AEs with an onset date that is on or after the first dose of study drug, and no more than 30 days after the last dose of RINVOQ and placebo if subject discontinued study drug prematurely.12

SAFETY CONSIDERATIONS

Consider the benefits and risks for the individual patient prior to initiating therapy with RINVOQ

WARNINGS AND PRECAUTIONS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death. These infections include tuberculosis (TB) and invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Carefully consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MORTALITY

In a large, randomized, postmarketing safety study comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years old with at least one cardiovascular (CV) risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ. In a large, randomized, postmarketing safety study comparing another JAK inhibitor with TNF blockers in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]), lymphomas, and lung cancer (in current or past smokers) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

Non-melanoma skin cancers have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

MAJOR ADVERSE CARDIOVASCULAR EVENTS

In a large, randomized, postmarketing study comparing another JAK inhibitor with TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

 

THROMBOSIS

Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Many of these adverse events were serious and some resulted in death.

In a large, randomized, postmarketing study comparing another JAK inhibitor to TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of thrombosis was observed with the JAK inhibitor. Avoid RINVOQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ and be promptly evaluated.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal perforations have been reported in clinical studies with RINVOQ. RINVOQ should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). Promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation.

LABORATORY ABNORMALITIES

Neutropenia: Treatment with RINVOQ was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3).

Lymphopenia: Absolute lymphocyte counts (ALC) <500 cells/mm3 were reported in RINVOQ clinical studies.

Anemia: Decreases in hemoglobin levels to <8 g/dL were reported in RINVOQ clinical studies.

Lipids: Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol.

Liver enzyme elevations: Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo.

EMBRYO-FETAL TOXICITY

Based on findings in animal studies, RINVOQ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose. Verify pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.

VACCINATION

Use of live, attenuated vaccines during, or immediately prior to, RINVOQ therapy is not recommended. Prior to initiating RINVOQ, patients should be brought up to date with all immunizations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.

CONSISTENT SAFETY PROFILE
ACROSS RA AND PsA1

WELL-STUDIED SAFETY PROFILE ACROSS CLINICAL PROGRAMS IN PsA AND RA

Long-term Exposure2-4

Long Term Safety data in PsA and RA

*Included RINVOQ monotherapy and combination therapy with csDMARDs across 6 trials.
Included RINVOQ monotherapy and combination therapy with non-biologic and biologic DMARDs across 2 trials.

In RA studies, patients could advance or switch to RINVOQ from placebo, or be rescued to RINVOQ from active comparator or placebo as early as Week 12 depending on the study design.1

In PsA studies, all remaining placebo patients were switched to RINVOQ 15 mg QD or upadacitinib 30 mg QD (1:1 ratio) at Week 24.1

Adverse reaction rates observed in clinical trials and LTE studies may not predict rates observed in clinical practice.

RINVOQ 15 mg is the only approved dose in PsA.

Overall, the safety profile observed in patients with active PsA treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA.

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, and acne.1

TEAE=treatment emergent adverse event, defined as an adverse event with onset on or after first dose of study drug and up to 30 days after last dose of RINVOQ.4

Well-studied
safety profile

Most Common Adverse Reactions from RINVOQ Clinical Trials

PSORIATIC ARTHRITIS12

Most Common Adverse Reactions from SELECT-PsA 1 and
SELECT-PsA 2 (24 Weeks)

Adverse reactions reported in ≥1% of psoriatic arthritis patients treated with
RINVOQ 15 mg pooled from the placebo‑controlled studies.

Common adverse events

RINVOQ is indicated for TNFi-IR patients.

Infections

  • In the placebo-controlled studies SELECT-PsA 1 and SELECT-PsA 2 through 24 weeks, infections were reported in 33.5% of patients treated with placebo and 37.5% of patients treated with RINVOQ 15 mg.13

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, and acne.1

RHEUMATOID ARTHRITIS1

Most Common Adverse Reactions from SELECT-COMPARE, SELECT-NEXT, and SELECT-BEYOND (12 Weeks)1

Adverse reactions reported in ≥1% of moderate to severe rheumatoid arthritis patients treated with RINVOQ 15 mg pooled from the placebo-controlled studies.

Common adverse events

RINVOQ is indicated for TNFi-IR patients.

Infections

  •  In the placebo-controlled study SELECT-COMPARE, SELECT-NEXT, and SELECT-BEYOND through 12/14 weeks, infections were reported in 20.9% of patients treated with placebo and 27.4% of patients treated with RINVOQ 15 mg.1
  •  In the 12-month exposure dataset, the incident rate of infection was 83.8 per 100 patient years for patients treated with RINVOQ 15 mg.1

ADVERSE REACTIONS: The most common adverse reactions in RINVOQ clinical trials (≥1%) were: upper respiratory tract infection, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, and acne.1

Lab Monitoring and treatment
considerations1

RINVOQ Lab Monitoring

Treatment with RINVOQ should not be initiated, or should be interrupted if:

Absolute neutrophil count
<1000 cells/mm3,*

Absolute lymphocyte count
<500 cells/mm3,*

Hemoglobin levels
<8 g/dL*

Liver enzyme elevations
and a
drug-induced liver
injury is suspected

Patient develops a serious
or opportunistic infection

*Treatment can be initiated or restarted after levels return above specified values, drug-induced liver injury diagnosis is excluded, or infection is controlled.

No dose adjustment is required for mild, moderate, or severe renal impairment.1

No dose adjustment is required for mild or moderate hepatic impairment.1

RINVOQ has not been studied in subjects with end-stage renal disease.1

RINVOQ is not recommended for use in patients with severe hepatic impairment.1

Serious Infections:1 Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ.

Tuberculosis (TB):1 Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.

Viral Reactivation:1 Screening and monitoring for viral hepatitis and herpes zoster reactivation should be performed in accordance with clinical guidelines before starting and during therapy with RINVOQ. If a patient develops herpes zoster, consider temporarily interrupting RINVOQ until the episode resolves.

Embryo-Fetal Toxicity:1 Based on animal studies, RINVOQ may cause fetal harm when administered to pregnant women. Verify pregnancy status prior to starting treatment. Advise women to use effective contraception during and for 4 weeks after completion of treatment.

Lab Abnormalities from the Placebo-Controlled Period of the PsAa and RAb Programs1,13,c

Neutropenia: Decreases in absolute neutrophil count (<1000 cells/mm3) occurred in 0.9% of patients treated with RINVOQ in PsA and 1.1% of patients treated with RINVOQ in RA in the first 3 months of exposure.

Lymphopenia: Decreases in lymphocyte counts (<500 cells/mm3) occurred in 1.3% of patients treated with RINVOQ in PsA and 0.9% of patients treated with RINVOQ in RA in the first 3 months of exposure.

Anemia: Hemoglobin decreases below 8 g/dL in at least one measurement occurred in 1.1% of patients treated with RINVOQ in PsA and <0.1% of patients treated with RINVOQ in RA in the first 3 months of exposure. 

Lipid Elevations: Increases in lipid parameters including total cholesterol, triglycerides, low‑density lipoproteins (LDL), and high‑density lipoproteins (HDL) were observed in patients treated with RINVOQ. Elevations in LDL and HDL cholesterol peaked by Week 8 and remained stable thereafter.

Liver Enzyme Elevations: Increases in liver enzyme levels >3 times the upper limit of normal (ULN) were observed in patients treated with RINVOQ.

Creatine Phosphokinase Elevations: Increases in creatine phosphokinase (CPK) levels >5 times the upper limit of normal were observed in patients treated with RINVOQ. Most elevations >5 times ULN were transient and did not require treatment discontinuation.

RINVOQ™ COMPLETE

Discover how RINVOQ Complete can provide
exceptional access and product support

IMPORTANT SAFETY INFORMATION & INDICATIONS1

INDICATIONS1

RINVOQ is indicated for the treatment of:

  • Moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.
  • Active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Limitation of Use: Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.

SERIOUS INFECTIONS

  • Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent TB infection prior to RINVOQ use.
  • Invasive fungal infections, including cryptococcosis and pneumocystosis.
  • Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

EMBRYO-FETAL TOXICITY

VACCINATION

LACTATION

HEPATIC IMPAIRMENT

ADVERSE REACTIONS

REFERENCES

  1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
  2. Cohen SB, Van Vollenhoven R, Curtis JR, et al. Integrated safety profile of upadacitinib with up to 4.5 years of exposure in patients with rheumatoid arthritis. Presented at: The European Congress of Rheumatology, 2-5 June 2021, E‑Congress.
  3. Burmester GR, Winthrop K, Blanco R, et al. Safety Profile of Upadacitinib Up to 3 Years in Patients with Psoriatic Arthritis: An Integrated Analysis from the Phase 3 Program. Presented at: The European Congress of Rheumatology, 2-5 June 2021, E‑Congress.
  4. Data on File. ABVRRTI71618.
  5. Mease PJ, Lertratanakul A, Anderson JK, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. 2020;80(3):312-320.
  6. van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderately-to-Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Multicenter, Multi-Country, Randomized, Double-Blind, Active Comparator-Controlled Trial. Arthritis Rheumatol. 2020;72(10):1607‑1620. doi:10.1002/art.41384
  7. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2‍30‍3‑2‍31‍1.
  8. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2‍50‍3‑‍2‍51‍2
  9. Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase 3, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. July 2019. doi:10.1002/art.41032.
  10. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):25‍1‍3‑‍25‍2‍4.
  11. Rubbert Roth A, Enejosa J, Pangan AL, et al. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. NEJM. 2020;383(16):1511‑1521.
  12. Data on File. ABVRRTI71873.
  13. Burmester G, Winthrop K, Nash P, et al. Safety Profile of Upadacitinib in Psoriatic Arthritis: Integrated Analysis from Two Phase 3 Trials [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10).
  14. Data on File. ABVRRTI69047.

INDICATIONS & LIMITATION OF USE1

RINVOQ is indicated for the treatment of:

  • Moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more
    TNF blockers.
  • Active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.

IMPORTANT SAFETY INFORMATION1

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant

IMPORTANT SAFETY INFORMATION1

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant

INDICATIONS & LIMITATION OF USE1

RINVOQ is indicated for the treatment of:

  • Moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more
    TNF blockers.
  • Active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.

IMPORTANT SAFETY INFORMATION1

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant

IMPORTANT SAFETY INFORMATION1

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant

IMPORTANT SAFETY INFORMATION & INDICATIONS1

INDICATIONS1

RINVOQ is indicated for the treatment of:

  • Moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.
  • Active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Limitation of Use: Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended.

SERIOUS INFECTIONS

  • Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent TB infection prior to RINVOQ use.
  • Invasive fungal infections, including cryptococcosis and pneumocystosis.
  • Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

EMBRYO-FETAL TOXICITY

VACCINATION

LACTATION

HEPATIC IMPAIRMENT

ADVERSE REACTIONS