11.4 Drugs Used in the Treatment of Multiple Sclerosis

Adverse Effects and Contraindications

Avonex is produced by recombinant DNA technology using genetically engineered Chinese hamster ovary cells into which the human interferon beta gene has been introduced. Betaseron is manufactured by bacterial fermentation of a strain of Escherichia coli that possesses the gene for human interferon beta. In addition, the medication contains mannitol and albumin. Anyone with a hypersensitivity to any of these three components could develop angioedema or anaphylaxis (DailyMed, Betaseron, 2023).

Flu-like symptoms on treatment days are common when first started. Symptoms experienced are fever, chills, myalgia, malaise, and sweating. These usually diminish over time. The symptoms can be minimized by starting with a low dose and then slowly titrating up to the full dose or by giving an analgesic/antipyretic medication before taking the interferon. Neutralizing antibodies can form against synthetic agents. This will decrease the drug’s effectiveness but also increase the risk of anaphylaxis.

Drug-induced lupus erythematous has been reported. Clinical manifestations include rash, polyarthritis, nephritis, and serositis. If this occurs, the drug should be stopped. Interferon beta can injure the liver by causing an asymptomatic increase in circulating liver enzymes. Liver function tests must be monitored routinely. If liver injury is evident, the dose can be decreased or a temporary interruption of treatment could be tried. When the liver function returns to baseline, treatment can resume with continued careful monitoring (DailyMed, Betaseron, 2023).

Transient injection site reactions include redness, pain, swelling, itching, or a lump. Injection site necrosis can occur with this drug, and some lesions have extended to the fascia overlying the muscle. Some have developed injection site abscesses and cellulitis, but this is usually the result of poor technique.

With interferon alpha, clients can develop subclinical hypothyroidism. It first causes inflammation of the thyroid (thyroiditis) that causes a short period of hyperthyroidism followed by hypothyroidism. Symptoms of heart failure can be exacerbated. Although these drugs have no direct-acting cardiac toxicity properties, they can trigger symptoms to arise.

Other immunosuppressive agents may increase the toxic effects of both immunosuppressives and elevate the risk of serious infection. Infections are related to the immunosuppressant effects. Many of these are opportunistic and are produced by microbes that do not normally cause infections unless the host is immunocompromised. Live vaccines should be avoided due to increased risk of vaccine-related infections. If needed, clients should receive them at least 4–6 weeks before starting therapy, especially the varicella-zoster virus (VZV) vaccine if one did not have chickenpox. Overall, the immunosuppression decreases the body’s response to vaccines and renders them useless (DailyMed, Betaseron, 2023).

Table 11.15 is a drug prototype table for interferons featuring interferon beta-1b. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following for clients who are taking interferons:

• Closely examine the injection sites for redness, swelling, and/or tenderness.
• Explain to the client the importance of avoiding contact with infected or sick people.
• Monitor the following lab studies before starting the medication and periodically throughout therapy: complete blood cell count (CBC) with differential, thyroid function, and liver function tests.
• Assess for any signs of infection or excessive bleeding or easy bruising.
• Emphasize to the client to avoid injuries and apply direct pressure to the affected area for several minutes.
• Teach the client signs and symptoms of hypo- and hyperthyroidism.
• Medicate with analgesics-antipyretics on injection days to decrease flu-like symptoms.
• Evaluate for any indication of depression or suicidal ideations.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Adverse Effects and Contraindications

Teriflunomide is very hepatoxic throughout therapy. If the alanine aminotransferase (ALT) amount is three times the upper normal limit on two consecutive tests, the drug must be immediately stopped, and an accelerated elimination procedure will begin. This procedure includes the administration of cholestyramine or activated charcoal for 11 days. In addition, this drug is highly teratogenic, and a negative pregnancy test must be obtained before therapy. The client should avoid pregnancy and speak with their provider if they are planning on becoming pregnant. Teriflunomide is eliminated very slowly and can take months to be fully leave the body.

Clients should be screened for latent tuberculosis (TB) before beginning therapy with immunomodulators because they have been found to activate latent TB, causing an active TB infection to develop. If found to be positive, the client must be treated for the active TB before initiating immunomodulators.

This group of drugs can cause peripheral neuropathy—either mononeuropathy or polyneuropathy. Risk factors include being older than 60 years of age, concurrent neurotoxic medications, and diabetes. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome has been associated with the use of this drug and is characterized by multiorgan hypersensitivity. DRESS can include symptoms like fever, rash, enlarged lymph nodes, facial swelling, hepatitis, nephritis, myocarditis, or myositis. Blood pressure should be checked before therapy and periodically throughout. An elevated blood pressure should be properly managed.

Concurrent use of drugs that have immunosuppressive and/or bone marrow suppressive properties should be avoided because it can increase the risk of infections. Teriflunomide can decrease the peak international normalized ratio (INR) by 25% in clients taking warfarin. Close monitoring of the INR is warranted to evaluate for warfarin dose adjustments to maintain therapeutic levels. This drug can also reduce the effectiveness of some oral contraceptives; therefore, a second barrier backup plan should be in place. In addition, the HMG-Co-A reductase inhibitors are prevented from being metabolized and can build up in the body. Live vaccines should be avoided because they can increase the risk of infection. These vaccines should be held until 6 months after immunomodulators have been discontinued.

Table 11.17 is a drug prototype table of immunomodulators featuring teriflunomide. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following for clients who are taking immunomodulators:

• Monitor the following lab values at baseline and routinely during therapy: ALT, aspartate aminotransferase (AST), serum bilirubin levels, CBC with differential.
• Observe for any signs and symptoms of infection and teach the client ways to prevent infection.
• Teach clients of reproductive age that they should use an effective contraceptive barrier.
• Monitor temperature and blood pressure during therapy.
• Perform a tuberculin skin test or interferon-gamma release assay (IGRA) to rule out latent TB before drug therapy is initiated.
• Obtain a pregnancy test before the start of treatment.
• Observe for any skin rashes/reactions.
• Monitor for any signs of bleeding, such as multiple bruises, hematuria, blood in the stool, or epistaxis.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Adverse Effects and Contraindications

Alemtuzumab must be administered in a certified health care setting with appropriate equipment to manage anaphylaxis or other serious infusion reactions, such as myocardial ischemia, myocardial infarction, ischemic/hemorrhagic stroke, and cervicocephalic arterial dissection. These can occur following any of the doses being given. To reduce infusion-related adverse effects, clients should be premedicated with high-dose corticosteroids for the first 3 days of each treatment course. They can also receive antihistamines and/or antipyretics before the dose. Additionally, antiviral agents should be administered for herpetic prophylaxis starting on the first day of dosing and continue for a minimum of 2 months after completion of alemtuzumab dosing or until the CD4+ lymphocyte count is less than 200 cells/microliter.

Some autoimmune disorders caused by alemtuzumab include immune thrombocytopenia (spontaneous bleeding, petechiae, heavy menstrual bleeding, hemoptysis), glomerular nephropathies (edema, decreased urine output, hematuria), autoimmune hemolytic anemia (chest pain, jaundice, dark urine, tachycardia), and thyroiditis.

Clients of childbearing age should consistently use effective contraception during therapy and for 4 months after a course of treatment. This drug can cause fetal harm.

A few infections caused by alemtuzumab include hepatitis, human papilloma virus (HPV), TB, and fungal infections, especially oral and vaginal candidiasis. Any client with active disease of these infections should not take the monoclonal antibodies. Pregnant or breastfeeding clients should avoid monoclonal antibodies.

The FDA recommends that 6 weeks before starting therapy, clients should be vaccinated for VZV. No live-virus vaccines should be received after starting monoclonal antibodies.

Oletuzemab can cause immune-mediated colitis characterized by diarrhea (DailyMed, Ocrevus, 2023). Other ADRs, contraindications, and cautions are similar to alemtuzumab.

Table 11.19 is a drug prototype table for monoclonal antibodies featuring alemtuzumab. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following when administering monoclonal antibodies:

• Obtain and analyze CBC with differential, serum creatinine levels, thyroid function, and urine cell count before therapy and then regularly until 48 months after last infusion.
• Obtain urine protein to creatinine ratio before the start of therapy.
• Assess client during and for 2 hours after each infusion, including vital signs, to identify any infusion-related adverse effects.
• Educate client regarding the drug’s increased risk of malignancies, including thyroid cancer, melanoma, and lymph disorders.
• Teach client signs and symptoms of hypothyroidism and hyperthyroidism.
• Perform a tuberculin skin test and HPV screening.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Adverse Effects and Contraindications

Initiation of S1P drug therapy results in a decrease in heart rate, for which monitoring is recommended. The nurse should administer the first dose in a setting in which resources to appropriately manage symptomatic bradycardia are available. Before dosing and at the end of the observation period, an ECG should be obtained for all clients. Observation of clients overnight is necessary if they are at higher risk of symptomatic bradycardia, heart block, prolonged QTc interval, or if taking drugs with known risk of torsades de pointes. If post-dose symptomatic bradycardia occurs, appropriate management should be initiated, beginning with continuous ECG monitoring and continuing until the symptoms have resolved.

Another adverse effect is macular edema. Fundoscopic examinations are essential before and 3–4 months after the treatment has been started. They are also performed again whenever a client reports visual disturbances. Diabetes mellitus and uveitis increase the risk of macular edema.

S1P receptor modulators may also cause fetal harm. Advise clients of childbearing age of the potential risk to a fetus and to use an effective method of contraception during treatment and for 10 days after stopping the drug.

Furthermore, siponimod fumaric acid can cause an increase in blood pressure readings. Blood pressure should be monitored routinely, and any significant changes should be reported to the provider. Suspicious skin lesions should be evaluated because the risk of basal cell carcinoma and melanoma is increased in clients being treated with siponimod fumaric acid.

There have been reported cases of posterior reversible encephalopathy syndrome (PRES) in clients receiving an S1P receptor modulator. This is caused by swelling and narrowing of the blood vessels within the brain. If a client complains of a sudden onset of a severe headache, altered mental status, vision changes, or seizure activity, the provider should promptly schedule a complete physical and neurological examination and consider an MRI. Symptoms are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, the drug should be discontinued.

Before initiation of treatment with siponimod fumaric acid, clients should be tested to determine their CYP2C9 genotype. Substantially elevated siponimod plasma levels may occur in clients who are homozygous for CYP2C9*3, so its use is contraindicated in these individuals.

This therapy can cause a dose-dependent reduction in peripheral lymphocyte count to 20%–30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. It is important not to start therapy in clients with active infection.

Avoid live vaccines during therapy and for 4 weeks after to prevent the possibility of developing an infection. Concurrently taking antineoplastics or immunosuppressive or immune-modulating therapies can elevate the client’s risk of infection. Class Ia or Class III antiarrhythmic drugs should be avoided due to the increased risk of prolongation of the QTc interval. The administration of drugs that slow the heart rate or decrease atrioventricular conduction (e.g., beta blockers, digoxin, diltiazem, or verapamil) can intensify the risk of dysrhythmias or atrioventricular block or can exacerbate manifestations of heart failure. Monitor for the development of severe increase in disability following drug discontinuation and begin appropriate treatment as needed.

Table 11.20 is a drug prototype table for S1P receptor modulators featuring siponimod fumaric acid. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following when administering S1P receptor modulators:

• Before starting treatment, obtain serum transaminases (ALT and AST), total bilirubin, CBC, and pulmonary function (e.g., spirometry) if indicated.
• Before starting treatment, determine whether clients are taking drugs that could slow their heart rate or atrioventricular (AV) conduction. Obtain cardiologist consultation before concomitant use with other drugs that decrease heart rate.
• Monitor all clients for 6 hours after the first dose for signs and symptoms of bradycardia with hourly heart rate and blood pressure measurement. Provider must assess for elevated blood pressures. Clients should know ahead of time they will be in the office for a minimum of 6 hours.
• Perform a thorough skin assessment periodically for signs of malignancy, such as asymmetry, indistinct borders, color variations, and increased size and elevation of any lesions.
• Assess for any neurological changes that could be related to PRES.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Centrally Acting Muscle Relaxant

Along with treating spasticity, baclofen is helpful in treating pain from trigeminal neuralgia that occurs in MS. This drug is available in oral and intrathecal (within the spine) forms and can be administered through an implantable delivery pump for treating central spasticity. The drug has no direct effect on skeletal muscle; therefore, it does not reduce muscle strength.

Peripherally Acting Muscle Relaxant

Dantrolene acts peripherally on the muscle itself. The drug inhibits the release of calcium from the sarcoplasmic reticulum directly within skeletal muscle cells. This action prevents the muscle fibers from contracting. Dantrolene does not interfere with neuromuscular transmission but does impair muscle strength. This drug is also used in the treatment and prevention of malignant hyperthermia (manages muscle contraction and rigidity). This agent is not therapeutic for treating muscle spasms associated with muscle injury or rheumatic disorders (DailyMed, Dantrolene, 2022).

Table 11.21 lists common muscle relaxants and typical routes and dosing for adult clients.

Adverse Effects and Contraindications

The most common adverse effects for baclofen are related to CNS depression. Constipation and urinary retention are linked to CNS depression of the parasympathetic nervous system reflexes. This slows down peristalsis and relaxes the detrusor muscle of the bladder. Baclofen crosses the placenta and enters breast milk, so a fetus/infant may develop CNS depression.

Cardiac concerns, such as heart failure and arrhythmias, result from the depression of the normal reflex arcs. This drug could exacerbate heart failure due to depressed muscle function caused by these drugs.

If the oral version of baclofen is stopped too quickly, this can cause the development of psychoses, visual hallucinations, and seizures. The drug should be tapered off over a 1- to 2-week period. Abrupt withdrawal of the intrathecal route can be more dangerous. Possible reactions include high fever, altered mental status, rebound spasticity, and muscle rigidity that could lead to muscle breakdown (rhabdomyolysis).

Blocking the spasticity associated with movement, posture, or balance results in loss of these functions. This places clients at high risk for falls.

Some common adverse reactions for dantrolene include diarrhea and abdominal cramps. Clients with respiratory depression must be closely monitored because this can be exacerbated by muscular weakness. Dose-related hepatotoxicity is the most serious adverse effect. Baseline liver enzymes should be obtained and monitored periodically throughout treatment. If clients show no response within 45 days of initiating this drug, it should be stopped to prevent damage to the liver. Caution should be used in all clients older than 35 years of age due to their increased risk of potentially fatal hepatocellular disease. Supplemental estrogen increases the incidence of hepatocellular toxicity. This drug should be discontinued at the first indication of hepatic impairment (DailyMed, Baclofen, 2023).

Table 11.22 is a drug prototype table for muscle relaxants featuring baclofen. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following for clients who are taking muscle relaxants:

• Assess alertness, orientation, and affect.
• Evaluate muscle strength before and after administration of medication.
• Auscultate bowel sounds and monitor bowel movements due to constipation and to avoid a fecal impaction.
• Obtain baseline liver function tests and serum BUN/creatinine levels and assess these levels periodically during therapy to assess for changes.
• Ensure safety precautions are in place to prevent falls because of fatigue, weakness, and confusion.
• Provide additional measures to relieve discomfort such as heat, rest, NSAIDs, and positioning to augment effects of the drug.
• Emphasize to the client/caregiver that the drug must be gradually discontinued over a 1- to 2-week period.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Adverse Effects and Contraindications

Hypersensitivity reactions have occurred with GABA structural analogs. Angioedema is characterized by swelling of the face, tongue, lips, gums, throat, and larynx. The drug should immediately be discontinued at the first sign of angioedema or other hypersensitivity reaction, such as hives, rash, wheezing, or dyspnea. Weight gain, due to an increased appetite, can be significant; some clients gain 7% or more in a few months. There is a possibility of rhabdomyolysis, so clients should be taught to let the provider know if muscle pain/tenderness occurs. Decreased sperm counts, reduced sperm motility, and increased sperm abnormalities can occur in male clients taking the drug. Clients may develop a low platelet count (thrombocytopenia).

Also, it has been reported pregabalin causes subjective effects similar to diazepam, increasing the risk of physical dependence. To avoid withdrawal symptoms, such as headache, diarrhea, or insomnia, the drug should be discontinued over at least 1 week.

CNS depressants and alcohol can increase the depressant effects of pregabalin. Taking angiotensin-converting enzyme (ACE) inhibitors concurrently increases the risk of swelling and hives. If taking thiazolidinediones with pregabalin, there is a higher chance of weight gain or swelling of one’s hands or feet.

Table 11.24 is a drug prototype table for GABA structural analogs featuring pregabalin. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following for clients who are taking GABA structural analogs:

• Ensure the client is taking an additional antiseizure medication because these are used only as adjuncts.
• Instruct the client not to break, chew, or crush the extended-release forms.
• Watch for any mood or personality changes and signs of suicidal ideation.
• Assess for seizure activity and ensure seizure precautions are in place.
• Evaluate for CNS depression to maintain client safety.
• Monitor weight and presence of peripheral edema.
• Emphasize to client not to stop drug abruptly.
• Assess client for muscle pain or tenderness.
• Monitor platelet count and creatinine kinase enzymes if muscle pain occurs.
• Evaluate history of drug use disorder or drug misuse.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.