Current treatments available for scleroderma patients

DISCLAIMER: The following information on treatment options for the symptoms of scleroderma do not in any way constitute therapeutic recommendations, prescriptions or endorsements. Consult your physician for the treatment regimen that is best suited for your individual condition.

There are a number of treatments available to address the various conditions associated with scleroderma. None of these is a cure – they are designed to treat symptoms of the disease. The different classes of drugs listed below are currently approved, either in the US or Europe, to treat each condition. All medications have side effects that vary in severity. If you are a patient taking a drug and experience any of the listed side effects, you should consult with a physician immediately.

Jump to: Joint Stiffness and Pain, Gastrointestinal Reflux, Intestinal Dysfunction, Renal (Kidney) Involvement and High Blood Pressure, Pulmonary Arterial Hypertension, Pulmonary Fibrosis (Alveolitis), Sjögren’s Syndrome

 

Raynaud’s Phenomenon

Calcium Channel Blockers

These medications are used to treat Raynaud’s phenomenon and reduce high blood pressure, a condition that increases the workload of the heart and arteries and can lead to malfunction of these organs. Calcium channel blockers affect the movement of calcium into the cells of the heart and blood vessels, increasing the supply of blood and oxygen to the heart while reducing the heart’s workload. These drugs can relax blood vessel muscles and may slow the heart rate.

Side effects: The most common side effects are swelling of ankles, feet or lower legs, low blood pressure, constipation and nausea. Calcium channel blockers may aggravate esophageal reflux. Less common are chest pain; dizziness, lightheadedness or fainting; and rash. Rare reactions include swelling of arms, face, legs, lips, tongue or throat; shortness of breath; rapid heart rate.

Form: Oral

Common brand names: nifedipine (Procardia®, Adalat®), amlodipine (Norvasc®), diltiazem (Dilacor XR®, Cardizem®, Tiazac®), verapamil (Calan®, Verelan®, Isoptin®), felodipine (Plendil®), nisoldipine (Sular®), bepridil (Vascor®), isradipine (DynaCirc®), nicardipine (Cardene®), nisoldipine (Sular®), prazosin (Minipress®)

 

Angiotensin II Receptor Antagonists

These drugs relax blood vessels by blocking the action of a natural chemical inside the body that narrows blood vessels, leading to high blood pressure.

Side effects: Headache is most common; less common are cough, fever or sore throat, dizziness, back pain, nasal congestion.

Form: Oral

Common brand names: losatan (Cozaar®), valsartan (Diovan®)

 

Angiotensin Converting Enzyme (ACE) Inhibitors

ACE inhibitors block the formation of an enzyme in the body that narrows blood vessels. This causes the blood vessels to relax and lowers blood pressure, increasing the supply of blood and oxygen to the heart.

Side effects: Swelling of face, mouth, hands or feet; dizziness, lightheadedness or fainting; skin rash, fever or joint pain. Confusion, irregular heartbeat, nervousness, numbness or tingling in hands, feet or lips, shortness of breath, difficulty breathing, weakness or heaviness of legs can be signs of too much potassium in the body, caused by the medication.

Form: Oral

Common brand names: captopril (Capoten®), benazepril (Lotensin®), lisinopril (Prinivil®, Zestril®), ramipril (Altace®), enalapril (Vasotec®)

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Joint Stiffness and Pain

NSAIDS

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to relieve some symptoms caused by arthritis (rheumatism), such as inflammation, swelling, stiffness and joint pain. For some people with certain medical conditions, NSAIDS can lead to the development of stomach bleeding and kidney disease. The risk is increased for people who take the product daily or regularly, particularly for those 65 and over or who take corticosteroids such as Prednisone.

Side effects: The most common side effects are abdominal or stomach cramps, pain or discomfort (mild to moderate); diarrhea (if taking mefenamic acid, stop taking it and check with your doctor immediately); dizziness, drowsiness or lightheadedness; headache (mild to moderate); heartburn, indigestion, nausea or vomiting.

Form: Oral

Common brand names: aspirin (Bayer®, St. Joseph’s®), ibuprofen (Advil®, Motrin®), naproxen (Naprosyn®, Aleve®), nabumeton (Relafen®), flurbiprofen (Ansaid®), fenoprofen (Nalfon®), diclofenac (Voltaren®, Cataflam®), meloxicam (Mobic®), diclofenac and misoprostol (Arthrotec®), diclofenac sodium (Voltaren®), etodolac (Lodine®), indomethacin (Indocin®), ketoprofen (Orudis®), ketorolac (Toradol®), oxaprozin (Daypro®), piroxicam (Feldene®), suldinac (Clinoril®)

 

COX-2 Inhibitors

These drugs work by blocking the COX-2 enzyme which is involved in the inflammation pathway. COX-2 inhibitors are used to relieve symptoms such as inflammation, swelling, stiffness and joint pain. They are a type of NSAID.

Caution: If you are using a non-steroidal anti-inflammatory drug (NSAID) such as celecoxib (Celebrex®), with an ACE inhibitor, some studies suggest that NSAIDs may reduce the effectiveness of the ACE inhibitor. Consult your physician.

Side effects: The most common side effects are back pain, dizziness, gas, headache, heartburn, insomnia, nausea, pain or burning in throat, stomach pain and stuffy or runny nose.

Form: Oral

Common brand names: celecoxib (Celebrex®)

 

Analgesics

Acetaminophen is an analgesic used to relieve pain (headaches, muscle aches) and reduce fever. Unlike aspirin, it does not relieve redness, stiffness or swelling, though it may relieve the pain caused by mild forms of arthritis. This medicine is available without a prescription; check with your physician, however, if you are taking other medications.

Using too much acetaminophen can lead to serious liver damage (this risk is increased in people who use alcohol regularly). Avoid taking multiple medications that contain acetaminophen.

Side effects: Though rare, check with your doctor as soon as possible if any of the following side effects occur: bloody or black, tarry stools; bloody or cloudy urine; fever with or without chills (not present before treatment and not caused by the condition being treated); pain in lower back and/or side (severe and/or sharp); pinpoint red spots on skin; skin rash, hives or itching; sores, ulcers or white spots on lips or in mouth; sore throat (not present before treatment and not caused by the condition being treated); sudden decrease in amount of urine; unusual bleeding or bruising; unusual tiredness or weakness.

Form: Oral

Common brand names: acetaminophen (Tylenol®, Datril®, Aceta®), tramadol (Ultram®)

 

Low-Dose Corticosteroids

These cortisone-like medicines are used to provide relief for inflamed areas of the body by lessening swelling, redness, itching and allergic reactions. They are often used as part of the treatment for a number of different diseases, such as severe allergies or skin problems, asthma or arthritis.

Caution: Corticosteroids are very strong medicines. In addition to their potential helpful effects, they have side effects that can be very serious. Glucocorticosteroids, also sometimes used to treat pulmonary fibrosis, have been found to increase risk of scleroderma renal crisis and should be used with caution and only in select cases under close observation such as frequent blood pressure checks. Be sure that you discuss the risks and benefits of this medicine with your doctor.

Corticosteroids may lower your resistance to infections and any infection you get may be harder to treat. Always check with your doctor as soon as possible if you notice any signs of a possible infection, such as sore throat, fever, sneezing or coughing.

Side effects: The most common side effects are increased appetite, indigestion, nervousness or restlessness. Less common or rare are darkening or lightening of skin color, dizziness or lightheadedness, flushing of face or cheeks, increased joint pain (after injection into a joint), increased sweating and/or the sensation of spinning.

Form: Oral; injected

Common brand name: Prednisone

 

Narcotics

Narcotic analgesics act in the central nervous system to relieve pain. Many of their side effects are also caused by actions in the central nervous system. When narcotics are used for long periods of time, your body may become dependent upon them and require higher dosage to relieve pain. They may also become habit-forming, causing mental or physical dependence. Physical dependence may lead to withdrawal symptoms when you stop taking the medicine.

Side effects: Dizziness, light-headedness or feeling faint, drowsiness, nausea or vomiting. Less common or rare side effects are blurred or double vision or other changes in vision, constipation (more common with long-term use and with codeine), decrease in amount of urine, difficult or painful urination, dry mouth, false sense of well-being, frequent urge to urinate, general feeling of discomfort or illness, headache, loss of appetite, nervousness or restlessness, nightmares or unusual dreams, redness, swelling, pain or burning at place of injection, stomach cramps or pain, trouble sleeping, unusual tiredness or weakness.

Form: Oral; patch; injection; suppository

Common brand names: acetaminophen/oxycodone (Percoset®), acetaminophen/hydrocone (Vicodin®), oxycodone hydrochloride (Oxycontin®, OxylR®)

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Gastrointestinal Reflux

Antacids

Antacids work by neutralizing excess stomach acid to relieve heartburn, sour stomach or acid indigestion. These medicines are available without a prescription. However, your doctor may have special instructions on the proper use and dose of these medicines.

Side effects: Chalky taste. Less common side effects are mild constipation, diarrhea and/or increased thirst.

Form: Oral

Common brand names: Maalox, Mylanta, Phillips, Gaviscon, Rolaids, Tums

 

H2 Blockers

Histamine H2-receptor antagonists, also known as H2-blockers, work by decreasing the amount of acid produced by the stomach. In over-the-counter strengths, these medicines are used to relieve and/or prevent heartburn, acid indigestion and sour stomach.

Side effects: Though uncommon, side effects may include constipation, diarrhea, difficult urination, dizziness, drowsiness, dryness of mouth or skin and/or headache.

Form: Oral

Common brand names: nizatidine (Axid®), famotidine (Pepcid®), cimetidine (Tagamet®), ranitidine (Zantac®)

 

Proton Pump Inhibitors

These medications decrease stomach acid production, minimizing gastrointestinal reflux disease, and help prevent esophageal ulcers.

Side effects: Though uncommon, side effects may include headache, diarrhea and/or constipation. Be aware of the increased risk of fractures of the hip, wrist and spine seen in some observational studies in patients using proton pump inhibitors.

Form: Oral

Common brand names: omeprazole (Prilosec®; Prilosec® OTC is available over-the-counter; Zegerid® is an immediate-release form of omeprazole), lansoprazole (Prevacid®), esomeprazole (Nexium®), rabeprazole (Aciphex®), pantoprazole (Protonix®)

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Intestinal Dysfunction

Prokinetic Agents

Metoclopramide is a medicine that increases the movements or contractions of the stomach and intestines. When given by injection, it is used to help diagnose certain problems of the stomach and/or intestines. Metoclopramide is also used, for a short time, to treat symptoms such as heartburn in patients who suffer esophageal injury from a backward flow of gastric acid into the esophagus.

Side effects: Diarrhea—with high doses, headache, drowsiness and/or restlessness. Less common are breast tenderness and swelling, changes in menstruation, constipation, increased flow of breast milk, mental depression, nausea, skin rash, trouble sleeping, unusual dryness of mouth and/or unusual irritability.

Form: Oral; injection

Common brand names: bethanecol (Urecholine®), metoclopramide (Reglan®)

 

Somatostatin Agonist

This medication, octreotide, is used for severe impairment of intestinal movement. Octreotide will be either injected subcutaneously (beneath the skin) or added to an intravenous drip for 15-30 minutes, one to four times a day. Your physician may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations.

Side effects: Side effects from octreotide are not common, though pain or burning at the injection site may last for up to 15 minutes. Tell your physician if any of these symptoms are severe or do not go away: upset stomach, vomiting, diarrhea, stomach pain, bloating, flatulence, loss of appetite or increased hunger.

Form: Intravenous

Common brand name: octreotide acetate (Sandostatin®)

 

Antibiotics

Reduced movement of the intestines can lead to bacterial overgrowth which in turn can lead to diarrhea and impaired absorption. The bacteria can be treated by antibiotics, which are best prescribed on a rotational basis to help prevent development of resistant strains.

Side effects: Nausea, vomiting, diarrhea and/or skin rash. Prolonged use may be complicated by superinfection—a condition produced by sudden growth of a type of bacteria, different from the original offenders.

Form: Oral; injection; intravenous

Common brand names: amoxicillin/clavulanate (Augmentin®), ampicillin, metronidazole (Flagyl®), tetracycline, vancomycin, ciprofloxacin (Cipro®), clarithromyacin (Biaxin®), azithromycin (Zithromax®)

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Renal (Kidney) Involvement and High Blood Pressure

Scleroderma patients generally have low blood pressure, so even modest increases in blood pressure could be a signal of an impending renal crisis and should be addressed immediately. The best way to treat renal crisis in scleroderma is to control the patient’s blood pressure, often with a short-acting ACE inhibitor such as captopril.

Angiotensin Converting Enzyme (ACE) Inhibitors

ACE inhibitors block the formation of an enzyme in the body that narrows blood vessels. This causes the blood vessels to relax and lowers blood pressure, increasing the supply of blood and oxygen to the heart.

Caution: Do not use ACE inhibitors if you are pregnant, intend to become pregnant or think you are pregnant. In pregnant women, ACE inhibitors can lower blood pressure to dangerously low levels and/or cause malformation of fetuses. For more information, see the package insert for the drug or contact your doctor. If you are using a non-steroidal, anti-inflammatory drug like celecoxib (Celebrex®) while you are taking an ACE inhibitor, be aware that the NSAID may reduce the effectiveness of the ACE inhibitor to control hypertension. Consult your physician.

Side effects: Swelling of face, mouth, hands or feet; dizziness, lightheadedness or fainting; skin rash; fever or joint pain. Confusion, irregular heartbeat, nervousness, numbness or tingling in hands, feet or lips, shortness of breath, difficulty breathing, cough, weakness or heaviness of legs can be signs of too much potassium in the body, caused by the medication.

Form: Oral

Common brand names: captopril (Capoten®), benazepril (Lotensin®), lisinopril (Prinivil®, Zestril®) ramipril (Altace®), enalapril (Vasotec®), quinapril (Accupril®), fosinopril (Monopril®), moexipril (Univasc®), trandolapril (Mavik®)

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Pulmonary Arterial Hypertension

Pulmonary hypertension results from high blood pressure that occurs in the main artery that carries blood from the right side of the heart to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump blood through the lungs.

Prostaglandin Derivatives

Epoprostenol belongs to the group of agents called prostaglandins, which occur naturally in the body and are involved in many biological functions. Epoprostenol works by relaxing blood vessels and increasing blood to the lungs.

Side effects: With initial dosage adjustments and/or dosage excess: diarrhea, rapid heartbeat, headache, light-headedness or fainting, nausea, redness of face or neck (flushing) and/or vomiting. More common side effects are anxiety and/or nervousness; diarrhea; dizziness; flu or infection-like symptoms, such as chills, confusion, delirium, light-headedness or fainting, rapid heartbeat, fever and/or rapid, shallow breathing; headache; jaw pain (when chewing); local infection at the catheter site; pain at injection site; pain in muscles or bones; redness of face (flushing); unusual bleeding such as nosebleeds or bleeding gums or bruising.

Form: Epoprostenol must be administered continuously by a portable pump that is operated by a small computer. The medicine will be delivered directly to the heart through a catheter that will be inserted into a vein in the chest.

Common brand name: Flolan®

 

Treprostinil

Treprostinil also belongs to the prostaglandin group. It is used to treat symptoms of primary pulmonary hypertension by relaxing blood vessels and increasing the supply of blood to the lungs, thus reducing stress on the heart.

Side effects: Aside from infection from bacteria at the site of infusion, the most common include edema (swelling); accumulation of blood, and/or dry, red, hot or irritated skin and/or hardening of skin at infusion site; flushing, faintness, dizziness or lightheadedness. Less common are blurred vision, confusion, dizziness; sudden sweating; unusual tiredness or weakness.

Form: Must be administered by continuous intravenous infusion

Common brand name: Remodulin®

 

Iloprost

Iloprost is a stable, inhalable form of prostacyclin, an imitator of prostaglandin. Its relaxing effect on the blood vessels is similar to a prostaglandin. The advantage of inhaled iloprost is that it is introduced directly to the lungs, thus avoiding potential side effects to the rest of the body.

Side effects: Headache, cough, flushing, jaw pain, low blood pressure, spasm of jaw muscles and/or influenza-like syndrome.

Form: Inhaled

Common brand name: Ventavis®

 

Endothelin Receptor Antagonists

These drugs work by preventing a small protein, endothelin-1, from binding to its receptors. By blocking the endothelin receptors, the blood supply to the lungs increases and workload of the heart decreases.

Side effects: Possible serious side effects include liver toxicity and birth defects. Other side effects include blurred vision, confusion, dizziness, dark urine, faintness or lightheadedness, fever, chills, light colored stools, loss of appetite, nausea and vomiting, stomach pain, sudden sweating, unusual tiredness or weakness an/or yellow eyes or skin. Swelling is less common.

Form: Oral

Common brand names: bosentan (Tracleer®), ambrisentan (Letairis®), macitentan (Opsumit®), riociguat (Adempas®)

 

Phosphosdiesterase type 5 (PDE5) inhibitors

PDE type 5 inhibitors prevent the metabolism of a signaling molecule called cGMP. Treatment with a PDE type 5 inhibitor builds up cGMP. cGMP relaxes smooth muscles, so arterial blood flow increases in the lungs and pulmonary arterial hypertension decreases.

Caution: Do not take PDE type 5 inhibitors with nitroglycerin or other nitrates as the combination of drugs may lower blood pressure to dangerous levels.

Side effects: Headache, facial flushing, nosebleeds, insomnia and upset stomach. Less common side effects are bluish or blurred vision, or sensitivity to light.

Form: Oral

Brand name: sildenafil citrate (Revatio®), tadalafil (Adcirca®)

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Pulmonary Fibrosis (Alveolitis)

Anti-Fibrotic Agent

Pirfenidone is an orally active, anti-fibrotic and anti-inflammatory agent that inhibits the synthesis of TGF-beta, a chemical mediator that controls many cell functions including proliferation and differentiation, and plays a key role in fibrosis. It also inhibits the synthesis of TNF-alpha, a cytokine that is known to have an active role in inflammation.

Side effects: Possible serious side effects include liver toxicity. Call your doctor right away if you have unexplained symptoms such as yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea-colored) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, or feeling tired. Sensitivity to sunlight (photosensitivity) and rash. Stomach problems such as nausea, vomiting, diarrhea, indigestion, heartburn, and stomach pain. Tell your doctor right away if your stomach problems get worse or do not go away. Other side effects include, but not limited to feeling tired, headache, dizziness, and decreased or loss of appetite.

Form: Oral

Common brand names: pirfenidone (Esbriet®)

Tyrosine Kinase Inhibitor

Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) that targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly nintedanib* inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).

Caution: Nintedanib (OFEV®) can cause birth defects or death to an unborn baby. Women should not become pregnant while taking OFEV. Women who are able to become pregnant should use birth control during treatment and for at least 3 months after treatment. If you become pregnant while taking OFEV, tell your doctor right away.

Side effects: Possible serious side effects include Liver problems. Call your doctor right away if you have unexplained symptoms such as yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea colored) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal or feeling tired. Diarrhea, nausea, and vomiting. Tell your doctor if you have diarrhea, nausea, or vomiting or if these symptoms do not go away or become worse. Tell your doctor if you are taking over-the-counter laxatives, stool softeners, and other medicines or dietary supplements that can cause diarrhea. Heart attack. Tell your doctor right away if you have symptoms of a heart problem. These symptoms may include chest pain or pressure, pain in your arms, back, neck or jaw, or shortness of breath. Stroke. Tell your doctor right away if you have symptoms of a stroke. These symptoms may include numbness or weakness on one side of your body, trouble talking, headache, or dizziness. Bleeding problems. OFEV may increase your chances of having bleeding problems. Tell your doctor if you have unusual bleeding, bruising, or wounds that do not heal. Tell your doctor if you are taking a blood thinner, including prescription blood thinners and over-the-counter aspirin. Tear in your stomach or intestinal wall (perforation). OFEV may increase your chances of having a tear in your stomach or intestinal wall. Tell your doctor if you have pain or swelling in your stomach area. Other side effects include, but not limited to diarrhea, nausea, stomach pain, vomiting, liver problems, decreased appetite, headache, weight loss, and high blood pressure.

Form: Oral

Brand name: nintedanib (OFEV®)

Immunosuppressants

This class of drugs works by weakening the body's immune system so it will not attack a transplanted organ or the body’s own tissue in the case of autoimmune diseases.

Caution: Cyclophosphamide (Cytoxan®, Neosar®), mycophenolate mofetil (CellCept®), azathioprine (Imuran®) should not be given if you are pregnant, intend to become pregnant or think you are pregnant. These drugs have caused malformations in fetal development of rodents and rabbits. For more information, see the product insert, consult your physician or contact the drug manufacturer.

Side effects: These are very strong drugs with severe side effects. High blood pressure, kidney and liver problems may result. Some immunosuppressants may contribute to the development of new cancers. The body may be less able to fight infections. Common effects are bleeding and/or tender or enlarged gums. Less common are seizures, fever or chills, vomiting, frequent urination. Rare side effects are confusion, irregular heartbeat, numbness or tingling in hands, feet or lips, shortness of breath, difficult breathing, severe stomach pain, nervousness, unusual tiredness or weakness, weight loss.

Form: Oral; injected

Common brand names: cyclosporine (Neoral®, Sandimmune®), mycophenolate mofetil (CellCept®), azathioprine (Imuran®), methotrexate (Rheumatrex®, Trexall®), D-penicillamine (Cuprimine®, Depen®)

 

Alkylating agents

Cyclophosphamide is in a class of drugs known as alkylating agents, which slow or stop the growth of cancer cells in your body. Cyclophosphamide is used to treat leukemias, lymphoma, bronchogenic carcinoma, small cell lung carcinoma, and other types of cancer. It has been shown to be effective in scleroderma lung disease. Talk to your doctor about the possible risks of using this drug. (See Caution about possible pregnancy risks involved with Cyclophosphamide in Immunosuppressants).

Side effects: Thinned or brittle hair, darkened and thickened skin, blistering skin or acne, loss of appetite or weight, mouth blistering and/or fatigue. Cyclophosphamide may contribute to the development of new cancers.

Forms: Oral; injected

Common brand names: Cytoxan®, Neosar®

A note about Minocycline: A recent controlled trial of the antibiotic minocycline has led to the conclusion that the drug is not an effective therapy for scleroderma. Results of the study, published in the February 2004 issue of “Arthritis & Rheumatism,” showed a degree of change in the modified Rodnan skin thickness score (the measurement used to determine effectiveness of the drug) that is similar to what can be expected in the natural course of the disease.

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Sjogren’s Syndrome

Pilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical application. Pilocarpine increases saliva secretion in the mouth and is used in the treatment of dry mouth.

Side effects: Dizziness, headache, flushing, urinary frequency, nausea, excessive sweating, hypertension, tachycardia.

Forms: Oral

Common brand names: Pilocarpine hydrochloride (Salagen®), cevimeline hydrochloride (Evoxac®)

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