CNS Lupus Medication

Updated: Aug 22, 2017
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MD, DM  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

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Corticosteroids

Class Summary

Systemic corticosteroids may be prescribed for lupus symptoms.

Prednisone (Rayos)

Prednisone is useful for treating inflammatory and allergic reactions; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity.

Prednisolone (Prelone, Flo-Pred, Millipred)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.

Methylprednisolone (SoluMedrol, Depo-Medrol, A-Methapred, Medrol)

Methylprednisolone decreases inflammation by suppressing migration of PMNs and reversing increased permeability.

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Immunosuppressants

Class Summary

These agents are immunosuppressive and cytotoxic and anti-inflammatory agents. Cyclosporine and azathioprine have equivalent corticosteroid-sparing effects, but azathioprine may be considered first-line therapy since cyclosporine requires close monitoring of blood pressure and serum creatinine.

Mycophenolate (CellCept, Myfortic)

Mycophenolate inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production. Two formulations are available; they are not interchangeable. The original formulation, mycophenolate mofetil (CellCept) is a prodrug that, once hydrolyzed in vivo, releases the active moiety, mycophenolic acid. A newer formulation, mycophenolic acid (Myfortic), is an enteric-coated product that delivers the active moiety.

Methotrexate (Trexall, Rheumatrex, Otrexup)

Methotrexate is used for managing constitutional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation.

Cyclophosphamide

Cyclophosphamide is used for immunosuppression in cases of serious SLE organ involvement, especially severe CNS involvement, vasculitis, and lupus nephritis. This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Azathioprine (Imuran, Azasan)

Azathioprine is an immunosuppressant and a less toxic alternative to cyclophosphamide. It is used as a steroid-sparing agent in nonrenal disease. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity.

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Antimalarials

Class Summary

Antimalarials may work through numerous proposed mechanisms in SLE, mediating subtle immunomodulation without causing overt immunosuppression. They are useful in preventing and treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis. They also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE.

Hydroxychloroquine (Plaquenil)

This agent inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

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Immune Globulins

Class Summary

High-dose (1-2 g/kg IV) immune globulin may be considered for concomitant use with pulse-dose corticosteroids in those with severe AIHA.

Immune globulin intravenous (Carimune NF, Octagam, Gammaplex, Gammagard, Privigen)

Immune globulin intravenous is given as a temporary measure to increase platelets. It neutralizes circulating myelin antibodies through anti-idiotypic antibodies; downregulates proinflammatory cytokines, including interferon gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells while augmenting suppressor T cells; blocks the complement cascade; promotes remyelination; and may increase immunoglobulin G (IgG) in cerebrospinal fluid (10% of cases).

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Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary

These agents provide symptomatic relief for arthralgias, fever, and mild serositis. NSAIDs may cause elevated liver function test results in patients with active lupus. Additionally, concomitant administration with prednisone may increase risk of GI ulceration.

Ibuprofen (Advil, Motrin IB, Addaprin, IBU-200, NeoProfen)

Ibuprofen is the drug of choice for patients with mild-to-moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Anaprox, Naprelan, Naprosyn)

Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of the enzyme cyclooxygenase, resulting in prostaglandin synthesis.

Ketoprofen

Ketoprofen is used for the relief of mild-to-moderate pain and inflammation. Small doses are initially indicated in small and elderly patients and in those with renal or liver disease. Doses >75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe patient for response.

Diclofenac (Voltaren XR, Cataflam, Cambia, Zipsor, Zorvolex)

Diclofenac inhibits prostaglandin synthesis by decreasing activity of enzyme cyclo-oxygenase, which in turn decreases formation of prostaglandin precursors.

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Anticonvulsants

Class Summary

Many anticonvulsants are used to alleviate painful dysesthesias, which frequently accompany peripheral neuropathies. Although they have many different mechanisms of action, their use for alleviating neuropathic pain probably depends on their general tendency to reduce neuronal excitability.

Gabapentin (Neurontin, Gralise)

Gabapentin is a membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); paradoxically, it is thought not to exert an effect on GABA receptors. It appears to act via the alpha(2)delta-1 and alpha(2)delta-2 auxiliary subunits of voltage-gated calcium channels. Gabapentin is used to manage pain and provide sedation in neuropathic pain.

Pregabalin (Lyrica)

Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown; it is known to binds with high affinity to alpha2-delta subunits of calcium channels. In vitro, pregabalin reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium-channel function. It is approved by the US Food and Drug Administration (FDA) for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Lamotrigine (Lamictal)

Lamotrigine is a triazine derivative useful in the treatment of neuralgia. It inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. The manufacturer's recommendation for dosage adjustments should be followed.

Topiramate (Topamax, Qudexy XR, Topiragen, Trokendi XR)

The precise mechanism by which topiramate acts is unknown, but the following properties may contribute to efficacy: (1) electrophysiologic and biochemical evidence showing blockage of voltage-dependent sodium channels, (2) augmentation of GABA activity at some GABA-A receptor subtypes, (3) antagonism of the AMPA/kainate subtype of the glutamate receptor, and (4) inhibition of carbonic anhydrase, particularly isozymes II and IV.

Levetiracetam (Keppra, Keppra XR)

Levetiracetam is another new anticonvulsant being used to combat pain of peripheral neuropathies. The mechanism by which it alleviates pain is not known but is probably related to the fact that anticonvulsants generally reduce nerve irritability. Levetiracetam is not FDA-approved for this indication.

Phenytoin (Dilantin, Phenytek)

Phenytoin blocks sodium channels nonspecifically and therefore reduces neuronal excitability in sensitized C-nociceptors. It is effective in neuropathic pain but suppresses insulin secretion and may precipitate hyperosmolar coma in patients with diabetes. Its antineuralgic effects may derive from the blocking of posttetanic potentiation by reducing summation of temporal stimulation.

Carbamazepine (Tegretol, Carbatrol, Epitol, Equetro)

Carbamazepine is a sodium-channel blocker that typically provides substantial or complete relief of pain in 80% of individuals with both idiopathic and multiple sclerosis−associated trigeminal neuralgia within 24-48 hours. It reduces sustained high-frequency repetitive neural firing and is a potent enzyme inducer that can induce own metabolism. Because of the risk of potentially serious blood dyscrasias, a benefit-to-risk evaluation should be undertaken before administration of the drug is initiated.

Therapeutic plasma levels are between 4 and 12 µg/mL for analgesic and antiseizure response. Peak serum levels are reached in 4-5 hours. The serum half-life is 12-17 hours with repeated doses. Carbamazepine is metabolized in the liver to its active metabolite (i.e., epoxide derivative) with a half-life of 5-8 hours. Metabolites are excreted via feces and urine.

Oxcarbazepine (Trileptal, Oxtellar XR)

The pharmacologic activity of oxcarbazepine is primarily exerted by the 10-monohydroxy metabolite (MHD). Studies indicate that this drug may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Anticonvulsant effect also may occur by affecting potassium conductance and high-voltage activated calcium channels.

Pharmacokinetics are similar in older children (>8 years) and adults; young children (< 8 years) have 30-40% greater clearance than older children and adults. Children younger than 2 years have not been studied in controlled clinical trials. Oxcarbazepine is not FDA-approved for this indication.

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Tricyclic Antidepressants

Class Summary

Tricyclic antidepressants (TCAs) are effective in painful paresthesias. Whereas the drugs in this category are administered in similar dosages, their sedative properties vary. Amitriptyline may be given if the patient suffers from insomnia, whereas nortriptyline and desipramine are better choices when sedation becomes a problem.

Amitriptyline

Amitriptyline inhibits reuptake of serotonin and norepinephrine by the presynaptic neuronal membrane and thus may increase their synaptic concentrations in the central nervous system (CNS). The dosage may be increased slowly up to maximum of 125 mg/day. If no response is obtained, a different TCA may provide some benefit, but more often, it is preferable to use a drug from a different category (eg, an anticonvulsant).

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. It inhibits reuptake of serotonin and norepinephrine by the presynaptic neuronal membrane and thus may increase their synaptic concentrations in the CNS. The pharmacodynamic effects of nortriptyline (eg, desensitization of adenyl cyclase and downregulation of beta-adrenergic receptors and serotonin receptors) also appear to play role in its mechanisms of action.

Desipramine (Norpramin)

Neurotransmitter reuptake inhibitor for NE and serotonin; inhibits reuptake by neuronal membrane; may also downregulate beta-adrenergic receptors and serotonin receptors.

Duloxetine (Cymbalta)

Duloxetine is indicated for diabetic peripheral neuropathic pain. It is a potent inhibitor of neuronal serotonin and norepinephrine reuptake.

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Electrolytes

Class Summary

Intravenous calcium chloride or gluconate infusions restore serum calcium levels. Calcium chloride delivers 3 times more elemental calcium than calcium gluconate.

Calcium carbonate (Caltrate, Oysco 500, Calcium 600, Calcarb 600, Titralac)

Calcium carbonate is indicated to restore and maintain normocalcemia when hypocalcemia is not severe enough to warrant rapid replacement. Calcium carbonate moderates nerve and muscle performance by regulating the action potential excitation threshold.

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