Recombinant IFN-β1a

Avonex (Interferon beta-1a) is a 166 amino acid glycoprotein with a predicted molecular weight of approximately 22,500 daltons. It is produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of Avonex is identical to that of natural human interferon beta.

Using the World Health Organization (WHO) natural interferon beta standard, Second International Standard for Interferon, Human Fibroblast (Gb-23-902-531), Avonex has a specific activity of approximately 200 million international units (IU) of antiviral activity per mg of Interferon beta-1a determined specifically by an in vitro cytopathic effect bioassay using lung carcinoma cells (A549) and Encephalomyocarditis virus (ECM). Avonex 30 mcg contains approximately 6 million IU of antiviral activity using this method. The activity against other standards is not known. Comparison of the activity of Avonex with other Interferon betas is not appropriate, because of differences in the reference standards and assays used to measure activity.

Avonex in the past has arrived to patients as a 30 mcg Lyophilized Powder that had to be combined with a sterile liquid. Now for ease and safety it arrives to patients as a 30 mcg Prefilled Syringe that is ready to use.

30 mcg Lyophilized Powder Vial

A vial of Avonex is formulated as a sterile, white to off-white lyophilized powder for intramuscular injection after reconstitution with supplied diluent (Sterile Water for Injection, USP). Each vial of reconstituted Avonex contains 30 mcg of Interferon beta-1a; 15 mg Albumin (Human), USP; 5.8 mg Sodium Chloride, USP; 5.7 mg Dibasic Sodium Phosphate, USP; and 1.2 mg Monobasic Sodium Phosphate, USP, in 1.0 mL at a pH of approximately 7.3.

30 mcg Prefilled Syringe

A prefilled syringe of Avonex is formulated as a sterile liquid for intramuscular injection. Each 0.5 mL (30 mcg dose) of Avonex in a prefilled glass syringe contains 30 mcg of Interferon beta-1a, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP at a pH of approximately 4.8.

The recommended dosage of Avonex (Interferon beta-1a) is 30 mcg injected intramuscularly once a week. A 25 gauge, 1 inch needle for intramuscular injection may be substituted for the 23 gauge, 1 ¼ inch needle by the prescribing physician, if deemed appropriate.

FDA Aprroval: 17 May 1996.

Recombinant IFN-β1b

Betaseron (Interferon beta-1b) is a purified, sterile, lyophilized protein product produced by recombinant DNA techniques. Interferon beta-1b is manufactured by bacterial fermentation of a strain of Escherichia coli (E coli) that bears a genetically engineered plasmid containing the gene for human interferon beta _ser17.

The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta-1b has 165 amino acids and an approximate molecular weight of 18,500 daltons. It does not include the carbohydrate side chains found in the natural material.

The specific activity of Betaseron is approximately 32 million international units (IU)/mg Interferon beta-lb. Each vial contains 0.3 mg of Interferon beta-lb. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.

Lyophilized Betaseron is a sterile, white to off-white powder, for subcutaneous injection after reconstitution with the diluent supplied (Sodium Chloride, 0.54% Solution).

0.3 mg Lyophilized Powder Vial

Betaseron is supplied as a lyophilized powder containing 0.3 mg of Interferon beta-1b, 15 mg Albumin (Human), USP, and 15 mg Mannitol, USP. The drug is packaged in a clear glass, single-use vial (3 mL capacity). A pre-filled single-use syringe containing 1.2 mL of diluent (Sodium Chloride, 0.54% solution), two alcohol prep pads, and one vial adapter with attached 27 gauge needle are included for each vial of drug. Betaseron and the diluent are for single-use only. Unused portions should be discarded. Store at room temperature.

The recommended dose of Betaseron is 0.25 mg injected subcutaneously every other day.

Injection Site Necrosis

Injection site necrosis (ISN) has been reported in 4% of patients in controlled clinical trials. Typically, injection site necrosis occurs within the first four months of therapy, although post-marketing reports have been received of ISN occurring over one year after initiation of therapy. Necrosis may occur at a single or multiple injection sites. The necrotic lesions are typically three cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to subcutaneous fat. However, there are also reports of necrosis extending to and including fascia overlying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions debridement and, infrequently, skin grafting have been required.

FDA Aprroval: 23 July 1993.

Glatiramer acetate

Copaxone is the brand name for glatiramer acetate. Glatiramer acetate, the active ingredient of Copaxone, consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 5,000-9,000 daltons. Glatiramer acetate is identified by specific antibodies.

Chemically, glatiramer acetate is designated L-glutamic acid polymer with L-alanine, L-lysine and L-tyrosine, acetate (salt).

Prefilled Syringe

Copaxone injection is supplied as a single-use pre-filled syringe containing 1.0 mL of a clear, colorless to slightly yellow, sterile, non-pyrogenic solution containing 20 or 40 mg of glatiramer acetate and 40 mg of mannitol, USP in cartons of 30 single-use pre-filled syringes, alcohol preps (wipes) and instructions for use. The recommended storage condition for the Copaxone Injection is refrigeration 36 to 46°F (2 to 8°C).

Recommended Dose

COPAXONE is for subcutaneous (SubQ) use only. The dosing schedule depends on the product strength that is selected.

FDA Aprroval: 20 Dec 1996.

Glatiramer acetate

Glatopa is the generic equivalent of Copaxone (glatiramer acetate) 20mg. The FDA has approved Glatopa as substitutable for Copaxone 20mg; it is not substitutable for Copaxone 40mg.

Glatiramer acetate is a synthetic protein that simulates myelin basic protein, a component of the myelin that insulates nerve fibers in the brain and spinal cord. This drug seems to block myelin-damaging T-cells through a mechanism that is not completely understood.

Glatopa is approved by the FDA to reduce the frequency of relapses in patients with RRMS. It's also approved for use in individuals who have experienced a first clinical episode (clinically-isolated syndrome) and have MRI features that are consistent with MS.

FDA Aprroval: 16 April 2015.

Recombinant IFN-β1b

Rebif (interferon beta-1a) is a purified 166 amino acid glycoprotein with a molecular weight of approximately 22,500 daltons. It is produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of Rebif is identical to that of natural fibroblast derived human interferon beta. Natural interferon beta and interferon beta-1a (Rebif®) are glycosylated with each containing a single N-linked complex carbohydrate moiety.

Using a reference standard calibrated against the World Health Organization natural interferon beta standard (Second International Standard for Interferon, Human Fibroblast GB 23 902 531), Rebif has a specific activity of approximately 270 million international units (MIU) of antiviral activity per mg of interferon beta-1a determined specifically by an in vitro cytopathic effect bioassay using WISH cells and Vesicular Stomatitis virus. Rebif 8.8 mcg, 22 mcg and 44 mcg contains approximately 2.4 MIU, 6 MIU or 12 MIU, respectively, of antiviral activity using this method.

Rebif® (interferon beta-1a) is formulated asa sterile solution in a prefilled syringe intended for subcutaneous (sc) injection. Each 0.5 ml (0.5 cc) of Rebif® contain either 22 or 44 mcg of interferon beta-1a, 2 or 4 mg albumin (human) USP, 27.3 mg mannitol USP, 0.4 mg sodium acetate, Water for Injection USP. Each 0.2 ml (0.2 cc) of Rebif® contains 8.8 mcg of interferon beta-1a, 0.8 mg albumin (human) USP, 10.9 mg mannitol USP, 0.16 mg sodium acetate, and Water for Injection USP.

Rebif® is supplied as a sterile, preservative-free solution packaged in graduated, ready to use in 0.2 or 0.5 mL pre-filled syringes with 27-gauge, 0.5 inch needle for subcutaneous injection.

The following package presentations are available:

Rebif® (interferon beta -1a) Titration Pack
- Six Rebif 8.8 mcg pre-filled syringes and Six Rebif 22 mcg pre-filled syringes

Rebif® (interferon beta -1a) 22 mcg Pre-filled syringe
- One Rebif 22 mcg pre-filled syringe or
- Twelve Rebif 22 mcg pre-filled syringes

Rebif® (interferon beta -1a) 44 mcg Pre-filled syringe
- One Rebif 44 mcg pre-filled syringe or
- Twelve Rebif 44 mcg pre-filled syringes

Dosages of Rebif are 22 and 44 mcg injected subcutaneously three times per week.

FDA Aprroval: 23 Jul 1993 Brand Name Available: 2002.

Recombinant IFN-β1b

Extavia (interferon beta-1b) is a purified, sterile, lyophilized protein product produced by recombinant DNA techniques. Interferon beta-1b is manufactured by bacterial fermentation of a strain of Escherichia coli (E coli) that bears a genetically engineered plasmid containing the gene for human interferon beta _ser17.

The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta-1b has 165 amino acids and an approximate molecular weight of 18,500 daltons. It does not include the carbohydrate side chains found in the natural material.

The specific activity of Extavia is approximately 32 million international units (IU)/mg Interferon beta-1b. Each vial contains 0.3 mg of Interferon beta-1b. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.

Lyophilized Extavia is a sterile, white to off-white powder, for subcutaneous injection after reconstitution with the diluent supplied (Sodium Chloride, 0.54% Solution).

0.3 mg Lyophilized Powder Vial

Extavia is supplied as a lyophilized powder containing 0.3 mg of Interferon beta-1b, 15 mg Albumin (Human), USP, and 15 mg Mannitol, USP. Extavia and the diluent are for single-use only. Unused portions should be discarded. Store at room temperature.

The recommended dose of Extavia is 0.25 mg injected subcutaneously every other day.

Injection Site Necrosis

Injection site necrosis (ISN) has been reported in 4% of patients in controlled clinical trials. Typically, injection site necrosis occurs within the first four months of therapy, although post-marketing reports have been received of ISN occurring over one year after initiation of therapy. Necrosis may occur at a single or multiple injection sites. The necrotic lesions are typically 3 cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to subcutaneous fat. However, there are also reports of necrosis extending to and including fascia overlying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions debridement and, infrequently, skin grafting have been required.

Approval Dates

Extavia was approve in the EU May 27, 2008 and the US August 17, 2009.

Daclizumab

Zinbryta (daclizumab) is a laboratory-created monoclonal antibody. It's designed to inhibit certain inflammatory functions of T cells and increase important immune cells that help regulate the immune system. Zinbryta is approved by the FDA to treat adult patients with relapsing forms of MS. It should be reserved for people who have had an inadequate response to two or more disease-modifying medications.

Indications and Usage

Zinbryta is indicated for the treatment of adult patients with relapsing forms of MS. Because of its safety profile, the use of Zinbryta should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Recommended Dose

150 milligrams subcutaneous (SubQ) monthly injection.

FDA Aprroval: 28 May 2016.

Natalizumab

Tysabri (natalizumab) is a monoclonal antibody against VLA-4, a molecule required for immune cells to adhere to other cells, penetrate the blood brain barrier and enter the brain. Tysabri is used as monotherapy for the treatment of patients with relapsing forms of MS to delay the progression of physical disability and reduce the frequency of clinical relapses.

Tysabri is a recombinant humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. The molecular weight of natalizumab is 149 kilodaltons. Tysabri is supplied as a sterile, colorless, and clear to slightly opalescent concentrate for intravenous (IV) infusion.

Each 15 mL dose contains 300 mg natalizumab; 123 mg sodium chloride, USP; 17.0 mg sodium phosphate, monobasic, monohydrate, USP; 7.24 mg sodium phosphate, dibasic, heptahydrate, USP; 3.0 mg polysorbate 80, USP/NF, in water for injection, USP at pH 6.1.

Tysabri is also used to treat moderate to severe Crohn's disease in adults. It's usually given after other Crohn's disease medications have been tried without successful treatment of this condition.

The recommended dose of Tysabri is 300 mg IV infusion every four weeks. Dilute Tysabri concentrate 300 mg/15 mL in 100 mL 0.9% Sodium Chloride Injection, USP, and infuse over approximately one hour. Do not administer Tysabri as an IV push or bolus injection. Observe patients during the infusion and for 1 hour after the infusion is complete. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction.

Infuse Tysabri 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP over approximately one hour. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.

Warning

It carries a warning for a potentially fatal disease, progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability. For this reason only patients who have signed up for treatment under a controlled drug distribution program can get this treatment. Tysabri increases the risk of a serious viral infection of the brain that can lead to disability or death. This risk is higher if you have a weak immune system or are receiving certain medicines. It is important to call your doctor right away if you have symptoms such as change in your mental state, problems with speech or walking, or decreased vision. These symptoms may start gradually and get worse quickly.

Additional information can be found in the section entitled PML.

FDA Aprroval: 23 November 2004.

Fingolimod

Gilenya (fingolimod) receiving FDA approval makes it the first oral treatment indicated for relapsing forms of MS available in the US.

Gilenya is the first in a new class of drugs called sphingosine 1-phosphate receptor (S1PR) modulators. In MS, the immune system damages the covering that protects nerve fibers in the central nervous system (CNS), which includes the brain and spinal cord. Gilenya's novel mechanism is unknown, but it is thought to work by reducing the immune system’s attack on the CNS by retaining certain white blood cells (lymphocytes) in the lymph nodes. This prevents the white blood cells from reaching the CNS, where they could potentially attack the protective covering around the nerve fibers, resulting in less inflammatory damage to the nerve cells. The white blood cell retention is reversible if Gilenya treatment is stopped.

Gilenya is a prescription medicine used to treat relapsing forms of MS in adults. Gilenya can decrease the number of MS flare-ups (relapses). Gilenya does not cure MS, but it can help slow the build up of physical problems that MS causes.

The FDA regulatory application included data showing Gilenya 0.5 mg reduced relapses by 52% (P<0.001) at one year compared with interferon beta-1a IM (Avonex®), one of the most commonly prescribed treatments for MS. Gilenya also reduced disease activity as measured by the number of new and newly enlarged T2 lesions on MRI scans compared to interferon beta-1a IM (1.6 vs 2.6, respectively, P=0.002) at one year. Data from a two-year placebo-controlled study showed a reduction in relapse rate (54% reduction P<0.001, compared with placebo) and risk of disability progression among Gilenya patients (30% reduction confirmed at 3-month follow-up visit P=0.02, compared with placebo).

In both studies, treatment with Gilenya also resulted in statistically significant reductions in brain lesion activity as measured by MRI.

Rcommended dose

0.5 mg capsule taken daily.

FDA Aprroval: 21 September 2010.

Teriflunomide

Aubagio (teriflunomide), a pyrimidine synthesis inhibitor, is an oral compound that inhibits the function of specific immune cells that have been implicated in MS. It's related to leflunomide, a drug used to treat rheumatoid arthritis. Aubagio can inhibit a key enzyme required by white blood cells (lymphocytes) – which in turn reduces the proliferation of T and B immune cells that are active in MS and also inhibits the production of immune messenger chemicals by T cells.

Aubagio was approved by the FDA in September, 2012 for patients with relapsing forms of MS. In one phase III study involving 1088 people with relapsing forms of MS (796 completed the trial), oral Aubagio reduced relapses compared with placebo over at least 108 weeks. Of two different doses tested during the TEMSO trial (7 and 14 mg), the higher dose also slowed progression of disability. Both doses also had a favorable effect measures, including a smaller increase in total lesion volume and fewer new and actives lesions compared with placebo.

Recommended Dose

Aubagio (7 or 14 mg) is a tablet taken once per day by mouth, with or without food.

FDA Aprroval: 12 September 2012

Dimethyl Fumarate

Tecfidera (dimethyl fumarate) is an oral therapy contained in capsules taken two times per day. Tecfidera, formerly known as BG-12, a formulation that was developed specifically for use by people with multiple sclerosis. A chemically related compound, called Fumaderm (dimethyl fumarate and fumaric acid esters), has been used at higher doses for decades in Germany to treat acute flare-ups of psoriasis. Although its exact mechanism of action is not known, Tecfidera is thought to inhibit immune cells and molecules, and may have anti-oxidant properties that could be protective against damage to the brain and spinal cord.

Tecfidera was evaluated in two phase III clinical trials:

In the DEFINE trial, there was a significant reduction in the proportion of people on Tecfidera who experienced relapses at 2 years, compared with those on inactive placebo. For those on the approved twice-daily dose, 27% experienced relapses, versus 46% of those on placebo – a 49% reduction in the risk of relapse. All secondary outcomes were also met in the Tecfidera groups, including significant impact on disease activity detected with MRI, and reduction in the risk of confirmed progression of disability (detected by the EDSS, a standard scale that measures disability). The proportion of those who progressed over two years was 16% for twice-daily Tecfidera compared with 27% for placebo – a 38% reduction in the risk of disability.

In the CONFIRM trial, there was a significant reduction in the average annual number of MS relapses (annualized relapse rate, or ARR) in the Tecfidera groups compared with the placebo group. For those on the approved twice-daily dose, ARR was reduced by 44% compared with placebo. Results for secondary endpoints included significant reductions in disease activity on MRI and in the proportion of patients experiencing relapses in the Tecfidera groups compared with those in the placebo group. Disability progression was not reduced significantly in the Tecfidera groups compared with the placebo group in this trial.

Tecfidera has not been studied in people under the age of 18.

Tecfidera was approved by the FD) in 2013 as a first-line therapy for adults with relapsing forms of MS, which means that the FDA doesn't require that any other medication(s) be tried before Tecfidera is prescribed.

Recommended Dose

When treatment with Tecfidera is started, you will be given a one-week reduced starter dose (120 mg twice a day), and thereafter a maintenance dose (240 mg twice a day).

FDA Aprroval: 27 March 2013

Peginterferon-β1a

Plegridy (Peginterferon beta-1a) is a new therapy that belongs to the same interferon class as several medications that have been approved by the FDA for the treatment of people with relapsing forms of MS.

Peginterferon beta-1a is a “pegylated” form of interferon, meaning that polyethylene glycol is attached to the interferon molecules, which enables them to maintain biologic effects in the body for longer periods of time and allows for less frequent dosing. Plegridy is given by subcutaneous (under the skin) injections once every two weeks.

This medication is manufactured by a biotechnological process from one of the naturally-occurring interferons (a type of protein). It is made up of exactly the same amino acids (major components of proteins) as the interferon beta found in the human body. Peginterferon beta-1a is an interferon beta-1a to which a single, linear 20,000 dalton (Da) methoxy poly(ethyleneglycol)-O-2-methylpropionaldehyde molecule is covalently attached to the alpha amino group of the N-terminal amino acid residue.

Plegridy was shown after one year of a two-year phase III clinical trial to reduce the relapse rate significantly more than placebo in a study of 1500 people with relapsing MS, reaching the primary goal of the study. (Lancet Neurology, published online, April 30, 2014.)

[For the “ADVANCE” trial, investigators worldwide randomly assigned 1512 people with relapsing MS to one of three groups: placebo, peginterferon beta-1a 125 mg delivered subcutaneously (under the skin) every two weeks, or peginterferon beta-1a 125 mg delivered subcutaneously every four weeks. The primary objective of the study was to determine the effects of the drug versus placebo on the annualized relapse rate after 48 weeks. Secondary objectives included the effects on central nervous system damage as observed on MRI scans, and disease progression as measured by the EDSS disability scale.

125 mcg (micrograms) Single-Dose

Plegridy 125 mcg contains 125 mcg of interferon beta-1a plus 125 mcg of poly(ethylene glycol). Using the World Health Organization (WHO) International Standard for interferon beta, Plegridy has a specific antiviral activity of approximately 100 million International Units (MIU) per mg of protein as determined using an in vitro cytopathic effect assay. Plegridy 125 mcg contains approximately 12 MIU of antiviral activity. Plegridy contains no preservative.

Plegridy Pen Single-Dose Prefilled Pen

Plegridy Pen is composed of an autoinjector that surrounds a prefilled glass syringe containing 0.5 mL of a sterile solution in water for injection of 63, 94, or 125 mcg of peginterferon beta-1a, 15.8 mg of L-arginine HCl, 0.79 mg of sodium acetate trihydrate, 0.25 mg of glacial acetic acid, and 0.025 mg of polysorbate 20. The pH is approximately 4.8.

Plegridy Single-Dose Prefilled Syringe

A prefilled syringe of Plegridy for subcutaneous injection contains 0.5 mL of a sterile solution in water for injection of 63, 94, or 125 micrograms of peginterferon beta-1a, 15.8 mg of L-arginine HCl, 0.79 mg of sodium acetate trihydrate, 0.25 mg of glacial acetic acid, and 0.025 mg of polysorbate 20. The pH is approximately 4.8.

FDA Aprroval: 18 August 2014

Alemtuzumab

Lemtrada (alemtuzumab) is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) and it causes depletion of lymphocytes (white blood cells). It was originally approved, at a significantly higher dose, for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing MS.

The FDA approved Lemtrada based on the results of two large, phase III clinical trials that confirmed its ability to significantly reduce relapse rates over two years over standard subcutaneous dosing of Rebif® (interferon beta-1a, EMD Serono Inc. and Pfizer). One of the studies also suggested that Lemtrada may significantly reduce worsening of disability.

Lemtrada is given by intravenous infusion – for 5 consecutive days initially and for 3 consecutive days one year later. The prescribing information includes a boxed warning about the potential for serious or life-threatening autoimmune disorders, infusion reactions and malignancies. Lemtrada will only be available from certified prescribers, and patients will be enrolled in a Risk Evaluation and Mitigation Strategy (REMS) program to ensure that ongoing periodic monitoring will be maintained to detect potential problems.

Potential risks:

Prescribing information for Lemtrada includes a boxed warning about the potential for serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia (a rare bleeding condition) and anti-glomerular basement membrane disease (which impacts the kidneys). It also warns about serious and life-threatening infusion reactions (reactions occurring during or more than 24 hours after the administration of the medication), increased risk of malignancies (including thyroid cancer, melanoma, and blood cancers). Autoimmune thyroid disorders occurred in 34% of people treated with Lemtrada in clinical studies.

The most common adverse reactions noted in people who have taken Lemtrada include rash, headache, fever, nasal congestion, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, hives, itching, thyroid gland disorders, fungal infection, pain in joints, extremities and back, diarrhea, sinusitis, sore mouth and throat, tingling, dizziness, abdominal pain, flushing and vomiting.

FDA Aprroval: 14 November 2014.

Mitoxantrone

Mitoxantrone (mitoxantrone hydrochloride) formerly known by the brand name Novantrone, is a synthetic antineoplastic anthracenedione for intravenous use. Mitoxantrone, pronounced as (mye toe zan' trone), is a chemotherapy drug that carries the risk of serious cardiac side effects or cancer. Because of these serious side effects, physicians tend to reserve its use for more advanced or worsening cases of MS.

Mitoxantrone injection is used to decrease the number of symptom episodes and slow the development of disability in patients with certain forms of MS. Mitoxantrone injection is also used together with steroid medications to relieve pain in people with advanced prostate cancer who did not respond to other medications. Mitoxantrone injection is also used together with other medications to treat certain types of leukemia. Mitoxantrone injection is in a class of medications called anthracenediones. Mitoxantrone treats MS by stopping certain cells of the immune system from reaching the brain and spinal cord and causing damage. Mitoxantrone treats cancer by stopping the growth and spread of cancer cells.

Novantrone is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary-progressive, progressive-relapsing, or worsening relapsing-remitting MS (i.e., patients whose neurologic status is significantly abnormal between relapses). Novantrone is not indicated in the treatment of patients with Primary Progressive MS.

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.

Mitoxantrone is supplied as a concentrate that must be diluted prior to injection.