Actemra80 mg/4 ml

Actemra 80 mg/4 ml is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: Rheumatoid Arthritis (RA): Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). ... Read moreActemra 80 mg/4 ml is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: Rheumatoid Arthritis (RA): Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Giant Cell Arteritis (GCA): Adult patients with giant cell arteritis. Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) Polyarticular Juvenile Idiopathic Arthritis (PJIA): Patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis. Systemic Juvenile Idiopathic Arthritis (SJIA): Patients 2 years of age and older with active systemic juvenile idiopathic arthritis. Cytokine Release Syndrome (CRS): Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome.

Drugs used for Rheumatoid Arthritis

Actemra 80 mg/4 ml is a recombinant humanized anti-human interleukin 6 (IL 6) receptor monoclonal antibody of the immunoglobulin (Ig) IgG1 subclass. Actemra 80 mg/4 ml binds specifically to both soluble and membrane-bound IL 6 receptors (sIL 6R and mIL 6R), and has been shown to inhibit sIL 6R and mIL 6R-mediated signaling. Interleukin-6 is a multi-functional cytokine, produced by a variety of cell types involved in local paracrine function as well as regulation of systemic physiological and pathological processes eg, induction of immunoglobulin secretion, T-cell activation, induction of hepatic acute phase proteins and stimulation of haematopoiesis. Interleukin-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia. The possibility exists for Actemra 80 mg/4 ml to affect host defences against infections and malignancies. The role of IL-6 receptor inhibition in the development of malignancies is not known.

General (IV or SC Injection): Substitution by any other biological medicinal product requires the consent of the prescribing physician. For adult patients with RA, Actemra 80 mg/4 ml may be administered as an IV infusion or a SC injection. For patients with pJIA and sJIA, Actemra 80 mg/4 ml is administered as an IV infusion. Actemra 80 mg/4 ml IV formulation should be diluted by a healthcare professional with sterile 0.9% w/v sodium chloride solution using aseptic technique (see Caution for Usage). Actemra 80 mg/4 ml is recommended for IV infusion over 1 hr.Actemra 80 mg/4 ml SC formulation is administered with a single-use PFS+NSD or pre-filled pen. The 1st injection should be performed under the supervision of a qualified healthcare professional. The recommended injection sites (abdomen, thigh and upper arm) should be rotated and injections should never be given into moles, scars or areas where the skin is tender, bruised, red, hard or not intact.SC Injection: Adults: Rheumatoid Arthritis (RA): Recommended Dose: 162 mg given once every week as a SC injection. Actemra 80 mg/4 ml can be used alone or in combination with MTX and/or other DMARDs. Patients transitioning from Actemra 80 mg/4 ml IV therapy to SC administration should administer the 1st SC dose at the time of the next scheduled IV dose under the supervision of a qualified healthcare professional. Actemra 80 mg/4 ml SC formulation is not intended for IV administration.  Assess suitability of patient for SC home use and instruct patients to inform a healthcare professional if they experience symptoms of allergic reaction before administering the next dose. Patients should seek immediate medical attention if developing symptoms of serious allergic reactions

Rheumatoid Arthritis: Recommended Adult Intravenous Dosage: When used in combination with DMARDs or as monotherapy the recommended starting dose is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. Patients less than 100 kg weight: 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response Patients at or above 100 kg weight: 162 mg administered subcutaneously every week. Giant Cell Arteritis: Recommended Adult Subcutaneous Dosage: The recommended dose of Actemra 80 mg/4 ml for adult patients with GCA is 162 mg given once every week as a subcutaneous injection, in combination with a tapering course of glucocorticoids. A dose of 162 mg given once every other week as a subcutaneous injection, in combination with a tapering course of glucocorticoids, may be prescribed based on clinical considerations. Actemra 80 mg/4 ml can be used alone following discontinuation of glucocorticoids. Actemra 80 mg/4 ml subcutaneous formulation is not intended for intravenous administration.Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Recommended Adult Subcutaneous Dosage: The recommended dose of Actemra 80 mg/4 ml for adult patients with SSc-ILD is 162 mg given once every week as a subcutaneous injection.Polyarticular Juvenile Idiopathic ArthritisRecommended Intravenous PJIA Dosage Every 4 Weeks- Patients less than 30 kg weight: 10 mg per kg Patients at or above 30 kg weight: 8 mg per kg Recommended Subcutaneous PJIA Dosage- Patients less than 30 kg weight: 162 mg once every three weeks Patients at or above 30 kg weight: 162 mg once every two weeks Systemic Juvenile Idiopathic ArthritisRecommended Intravenous SJIA Dosage Every 2 Weeks- Patients less than 30 kg weight: 12 mg per kg Patients at or above 30 kg weight: 8 mg per kg Recommended Subcutaneous SJIA Dosage- Patients less than 30 kg weight 162 mg every two weeks Patients at or above 30 kg weight 162 mg every week Cytokine Release SyndromeRecommended Intravenous CRS Dosage- Patients less than 30 kg weight: 12 mg per kg Patients at or above 30 kg weight: 8 mg per kg Alone or in combination with corticosteroids.General Dosing Information: It is recommended that Actemra 80 mg/4 ml not be initiated in patients with an absolute neutrophil count (ANC) below 2000 per mm3, platelet count below 100,000 per mm3, or who have ALT or AST above 1.5 times the upper limit of normal (ULN). Actemra 80 mg/4 ml doses exceeding 800 mg per infusion are not recommended in RA or CRS patients.

Interactions with CYP450 Substrates: Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with Actemra 80 mg/4 ml may restore CYP450 activities to higher levels than those in the absence of Actemra 80 mg/4 ml leading to increased metabolism of drugs that are CYP450 substrates. In vitro studies showed that Actemra 80 mg/4 ml has the potential to affect expression of multiple CYP enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Its effect on CYP2C8 or transporters is unknown. In vivo studies with omeprazole, metabolized by CYP2C19 and CYP3A4, and simvastatin, metabolized by CYP3A4, showed up to a 28% and 57% decrease in exposure one week following a single dose of Actemra 80 mg/4 ml, respectively. The effect of Actemra 80 mg/4 ml on CYP enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of Actemra 80 mg/4 ml, in patients being treated with these types of medicinal products, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) and the individual dose of the medicinal product adjusted as needed. Exercise caution when coadministering Actemra 80 mg/4 ml with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of Actemra 80 mg/4 ml on CYP450 enzyme activity may persist for several weeks after stopping therapy

Hypersensitivity to Actemra 80 mg/4 ml or to any of the excipients.

Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, injection site reactions.

Pregnancy Category- C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risksLactation: Unknown whether distributed in breast milk, do not breast feed

Serious Infections- do not administer Actemra 80 mg/4 ml during an active infection, including localized infections. If a serious infection develops, interrupt Actemra 80 mg/4 ml until the infection is controlled. Gastrointestinal (GI) perforation- use with caution in patients who may be at increased risk. Hepatotoxicity- Monitor patients for signs and symptoms of hepatic injury. Modify or discontinue Actemra 80 mg/4 ml if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. Laboratory monitoring- recommended due to potential consequences of treatment-related changes in neutrophils, platelets, lipids, and liver function tests. Hypersensitivity reactions, including anaphylaxis and death have occurred. Live vaccines- Avoid use with Actemra 80 mg/4 ml.

There are limited data available on overdoses with Actemra 80 mg/4 ml. One case of accidental overdose was reported with intravenous Actemra 80 mg/4 ml in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.

Actemra 80 mg/4 ml must be refrigerated at 2ºC to 8ºC. Do not freeze. Protect the vials, syringes, and autoinjectors from light by storage in the original package until time of use, and keep syringes and autoinjectors dry.

Children: The safety and efficacy of Actemra 80 mg/4 ml in children with conditions other than pJIA or sJIA have not been established. Children Elderly: No dose adjustment is required in elderly patients ≥65 years.Renal Impairment: No dose adjustment is required in patients with mild renal impairment (see Pharmacology: Pharmacokinetics under Actions). Actemra 80 mg/4 ml has not been studied in patients with moderate to severe renal impairment. Hepatic Impairment: The safety and efficacy of Actemra 80 mg/4 ml has not been studied in patients with hepatic impairment (see Precautions).

Drugs used for Rheumatoid Arthritis

Actemra 80 mg/4 ml binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.

Based on animal data, may cause fetal harm. Discontinue drug or nursing taking into consideration importance of drug to mother.