How much prednisone should you take. What is considered a high dose of prednisone. How to take prednisolone tablets and liquid properly. What are the potential side effects of prednisone. How to safely stop taking prednisone.

Understanding Prednisone Dosage: From Low to High

Prednisone, a powerful corticosteroid, is prescribed in various doses depending on the medical condition and individual patient factors. To properly understand prednisone dosage, it’s crucial to recognize the different dose ranges:

• Low dose: Less than 7.5 mg per day
• Moderate dose: Between 7.5 mg and 40 mg per day
• High dose: 40 mg to 60 mg per day

While doses above 40 mg per day are generally considered high, it’s important to note that individual responses to prednisone can vary. In some cases, doctors may prescribe doses higher than 60 mg, typically administered intravenously for short periods.

Factors Influencing Prednisone Dosage

The prescribed dose of prednisone depends on several factors:

• The specific health problem being treated
• Whether it’s a short-term or long-term treatment
• The patient’s age, weight, and overall health condition
• The severity of symptoms

For children, dosages are typically calculated based on height and weight, resulting in lower doses compared to adults with the same condition.

Proper Administration of Prednisolone: Tablets and Liquid Forms

Prednisolone, a form of prednisone, comes in both tablet and liquid forms. Proper administration is crucial for effectiveness and minimizing side effects.

Tablet Administration

When taking prednisolone tablets:

• Take as a single dose once a day, preferably with breakfast
• Follow your doctor’s instructions on dosage
• For enteric-coated or gastro-resistant tablets, swallow whole and avoid taking indigestion medicines 2 hours before or after

Liquid Administration

Prednisolone liquid comes in two strengths:

• 1 mg per 1 ml
• 10 mg per 1 ml

Ensure you understand the correct dosage and use the provided measuring device for accuracy.

Timing Your Prednisone Dose for Optimal Effect

The timing of your prednisone dose can significantly impact its effectiveness and potential side effects. Here are key considerations:

• Morning dosage: Take prednisolone with breakfast to minimize stomach upset and reduce sleep disturbances
• Single daily dose: Unless otherwise instructed, take the entire daily dose at once
• Alternate day dosing: Some doctors may recommend taking prednisone every other day to reduce side effects

Is there a best time to take prednisone? For most patients, taking prednisone in the morning with breakfast is ideal. This mimics the body’s natural cortisol production rhythm and may help reduce side effects.

Managing Prednisone Side Effects: What to Watch For

While prednisone can be highly effective, it’s associated with various side effects, especially at higher doses or with long-term use. Common side effects include:

• Increased appetite and weight gain
• Mood changes, including irritability or euphoria
• Sleep disturbances
• Increased risk of infections
• Skin thinning and easy bruising
• Elevated blood sugar levels

Can prednisone side effects be mitigated? While some side effects are unavoidable, strategies such as taking the medication in the morning, maintaining a healthy diet, and regular exercise can help manage certain side effects. Always discuss concerns with your healthcare provider.

Tapering Off Prednisone: A Crucial Step for Safety

Abruptly stopping prednisone can be dangerous, particularly for those on high doses or long-term treatment. Tapering is essential to allow your body to adjust and resume its natural cortisol production.

Why Tapering is Important

Suddenly stopping prednisone can lead to withdrawal symptoms such as:

• Severe fatigue
• Weakness
• Body aches
• Joint pain

Additionally, abrupt discontinuation may cause a flare-up of the underlying condition being treated.

The Tapering Process

Your doctor will create a personalized tapering plan, which typically involves:

• Gradually reducing the dose over several weeks
• Regular check-ups to monitor your response
• Adjustments to the tapering schedule as needed

How long does it take to taper off prednisone? The duration of the tapering process varies depending on the initial dose and length of treatment. It can range from a few days for short-term use to several months for long-term, high-dose treatments.

Long-Term Prednisone Use: Balancing Benefits and Risks

While prednisone can be life-saving for many conditions, long-term use comes with potential risks that need careful consideration:

Potential Long-Term Side Effects

• Osteoporosis (bone thinning)
• Cataracts and glaucoma
• Increased risk of diabetes
• Muscle weakness
• Adrenal suppression

Are there alternatives to long-term prednisone use? In some cases, doctors may explore alternative treatments or combine prednisone with other medications to minimize long-term exposure. Regular monitoring and discussions with your healthcare provider are crucial for managing long-term prednisone therapy.

Special Considerations: Prednisone Use in Specific Populations

Certain groups require special attention when using prednisone:

Prednisone in Children

Children may be more susceptible to prednisone’s effects on growth and development. Dosages are carefully calculated based on weight and height, and growth is closely monitored.

Prednisone During Pregnancy and Breastfeeding

While prednisone can be used during pregnancy when benefits outweigh risks, it requires careful consideration. Low doses are generally considered safe during breastfeeding, but higher doses may require precautions.

Elderly Patients and Prednisone

Older adults may be more susceptible to side effects and may require lower doses or more gradual tapering.

How does age affect prednisone metabolism? As we age, our ability to metabolize medications can change. Elderly patients may clear prednisone more slowly from their system, potentially increasing the risk of side effects. This is why dosages are often adjusted for older patients.

Interactions and Precautions: Maximizing Prednisone Safety

To ensure safe and effective use of prednisone, be aware of potential interactions and necessary precautions:

Drug Interactions

Prednisone can interact with various medications, including:

• Blood thinners (e.g., warfarin)
• Certain antibiotics
• NSAIDs (e.g., ibuprofen)
• Diabetes medications

Always inform your healthcare provider about all medications, supplements, and herbal products you’re taking.

Dietary Considerations

While on prednisone:

• Monitor salt intake, as prednisone can cause fluid retention
• Ensure adequate calcium and vitamin D intake to support bone health
• Be mindful of calorie intake, as prednisone can increase appetite

Does prednisone affect vitamin absorption? Prednisone can impact the absorption and metabolism of various nutrients, particularly calcium and vitamin D. This is why supplementation is often recommended during treatment, especially for long-term use.

Lifestyle Adjustments

To minimize side effects and support overall health while on prednisone:

• Engage in regular weight-bearing exercise to maintain bone density
• Practice stress-reduction techniques to manage mood changes
• Maintain good sleep hygiene to counteract sleep disturbances

By understanding proper dosing, administration, potential side effects, and necessary precautions, patients can work effectively with their healthcare providers to maximize the benefits of prednisone while minimizing risks. Regular communication with your doctor is key to successful prednisone therapy, ensuring that your treatment plan is tailored to your specific needs and adjusted as necessary over time.

How and when to take prednisolone tablets and liquid

It’s important to take prednisolone as your doctor has advised.

Dosage and strength

The dose of prednisolone you’ll take depends on your health problem and whether you are taking it as a short course or for longer.

The usual dose varies between 5mg and 60mg daily but occasionally higher doses may be prescribed.

The strength of tablets range from 1mg to 25mg. There are 2 strengths of liquid with either 1mg or 10mg in every 1ml.

In children, the dose may be lower than for an adult with the same problem because it is calculated based on their height and weight.

Changes to your dose

Your dose may go up or down.

Once your health problem or condition starts to get better, it’s likely that your dose will go down.

Your doctor may reduce your dose before you stop treatment completely. This is to reduce the risk of withdrawal symptoms.

Your dose may go up if your symptoms get worse.

How to take it

Unless your doctor or pharmacist gives you different instructions, it’s best to take prednisolone as a single dose once a day, with breakfast. For example, if your dose is 40mg daily, your doctor may tell you to take 8 tablets (8 x 5mg) all at the same time.

Take prednisolone with breakfast so it does not upset your stomach. Taking prednisolone in the morning also means it’s less likely to affect your sleep.

If your prednisolone tablets are labelled as “enteric coated” or “gastro resistant”, you can take these with or without food but make sure to swallow them whole. Do not take indigestion medicines 2 hours before or after taking enteric coated or gastro resistant tablets.

Sometimes, your doctor may advise you to take prednisolone on alternate days only.

How long to take it for

This depends on your health problem or condition.

You may only need a short course of prednisolone for up to 1 week.

You may need to take it for longer, even for many years or the rest of your life.

If you forget to take it

If you miss a dose of prednisolone, take it as soon as you remember. If you do not remember until the following day, skip the missed dose and take the next one at the usual time.

Do not take a double dose to make up for a forgotten one.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

Stopping prednisolone

It can be dangerous to stop taking prednisolone suddenly, especially if you have been on a high dose for a long time.

Your health condition may flare up again. You may also get withdrawal side effects including:

• severe tiredness
• weakness
• body aches
• joint pain

These side effects are most likely to happen if you have taken prednisolone for more than a few weeks or you take more than 40mg daily.

Your doctor will probably want to reduce your dose gradually over several weeks to prevent these side effects.

Important

Do not stop taking prednisolone without talking to your doctor – you will need to reduce the dose gradually.

If you take too much

Taking too many prednisolone tablets is unlikely to harm you.

If you’re worried, talk to your doctor or pharmacist.

Page last reviewed: 24 February 2022

Next review due: 24 February 2025

What is considered a high dose of prednisone?

Medically reviewed by Sally Chao, MD. Last updated on Sep 1, 2021.

The starting dose of prednisone may be between 5 mg to 60 mg per day. A dose above 40 mg per day may be considered a high dose. However, everybody responds differently to prednisone, so what might be a high dose depends on the person and the condition.

In general:

• Low dose: less than 7.5 mg per day
• Moderate dose: between 7.5 mg and 40 mg per day
• High dose: 40 mg to 60 mg per day

Sometimes doses much higher than the upper limit of 60 mg are given through an IV for short periods.

Doctors prescribe prednisone at the lowest effective dose for the shortest possible time. If prednisone is not effective, it should be stopped as soon as possible. The dose and time need to be adjusted for each patient based on the condition and response to treatment.

The reason that prednisone is used with care is that prednisone can pose serious side effects and long-term risks. In patients who need longer dosing of prednisone, it may be given every other day. This may reduce side effects and complications.

Side effects

Common side effects from prednisone are due to the effect it has on lowering your immune system’s response to an infection. Prednisone also affects many other parts of your body. These effects may occur at high doses, or even lower doses if the treatment continues for a longer time. Side effects may include:

• Fluid retention that can lead to swelling, high blood pressure or heart failure
• Muscle weakness and loss of muscle
• Weakening of bones that can cause osteoporosis, spinal and long bone fractures or death of bone tissue
• Ulcers of the stomach or esophagus
• Swelling of the belly or inflammation of the pancreas
• Poor wound healing
• Effects on the skin may include thinning, bruising, redness, increased sweating and bleeding under the skin
• Effects on the nervous system may include headaches, dizziness, insomnia, mood swings, personality changes, depression and psychosis
• Effects on glands of the body may include irregular menstrual periods, slowed growth in children and high blood sugar
• Effects on the eyes may include cataracts, increased pressure inside the eyes, bulging eyes and glaucoma

Some people are at higher risk of adverse effects from higher doses or longer use of prednisone. These include people with:

• Hypothyroid disease
• Cirrhosis of the liver
• Herpes infection of the eye
• Mental health conditions
• Aspirin use
• Ulcerative colitis
• Ulcer disease
• Kidney failure
• An infected abscess
• High blood pressure
• Osteoporosis
• Recent intestinal surgery

Use of prednisone at any dose is not considered safe during pregnancy or breastfeeding. Vaccinations may need to be avoided if you are taking prednisone at high doses.

Prednisone is a powerful anti-inflammatory drug used to treat conditions of inflammation. Even a normal dose may be considered high for some people. It is important to always weigh the risks against the benefits when taking this medication.

References

1. U.S. National Library of Medicine DailyMed. Prednisone. December 2020. Available at: https://dailymed. nlm.nih.gov/dailymed/lookup.cfm?setid=263ed4fa-3c29-4abb-9cb1-bc016bd34a05&version=3#. [Accessed August 9, 2021].
2. American Osteopathic College of Dermatology (AOCD). Steroids (Oral). Available at: https://www.aocd.org/page/SteroidsOral. [Accessed August 13, 2021].
3. Drugs.com. Prednisone. December 2020. Available at: https://www.drugs.com/pro/prednisone.html. [Accessed August 9, 2021].

Related medical questions

• Is it OK to drink alcohol with Prednisone?
• How long can you take prednisone safely?
• Prednisone: What are 12 Things You Should Know?
• How long does it take for prednisone to work?
• What’s a good prednisone taper schedule?
• Do I take all 6 prednisone pills at once on the first day?
• Methylprednisolone vs Prednisone – How do they compare?
• How long does prednisone stay in your system?
• Prednisone vs Prednisolone – What’s the difference?
• Does prednisone cause a rapid heart rate?
• I just took ibuprofen and prednisone, is that ok?

Drug information

• Prednisone Information for Consumers
• Prednisone prescribing info & package insert
  (for Health Professionals)
• Side Effects of Prednisone
  (detailed)

Related support groups

• Prednisone
  (324 questions, 1,059 members)

Medical Disclaimer

Can prednisolone help with neuritis of the facial nerve?

Prednisolone, or Prednisone, like any other steroids, is aimed at reducing swelling and fighting inflammation in the acute phase. Neuritis of the facial nerve (Bell’s palsy) most often occurs as a result of compression due to swelling of adjacent tissues. Therefore, steroid drugs are most often used to combat the damaging factor that causes this swelling.

Does prednisolone help with acute neuritis of the facial nerve?

Steroids are NOT a specific medicine for facial neuritis (Bell’s palsy). This is very, very important to understand. Steroids help eliminate or reduce the damaging factor that causes paresis. Neuritis occurs as a result of damage to the facial nerve. Therefore, it is very important to consult a doctor as soon as the first symptoms of neuritis appear in order to start fighting the cause of the damage (inflammation, viral infection, swelling, etc.) as soon as possible. The duration and degree of subsequent recovery depends on the degree of damage to the facial nerve. Your doctor will prescribe medications, including steroids, that can help reduce the damaging factor and limit damage to the facial nerve. This is important to avoid prolonged recovery which can lead to complications and residual effects such as synkinesis.

How long should I take Prednisolone?

Steroids such as prednisone or prednisone have their own side effects. Therefore, you should not take them longer than necessary or directed by your doctor. In addition, once the damaging factor (edema, inflammation, viral infection, etc.) is eliminated, there is no longer any point in taking steroids. Steroids have no effect on the repair of damaged facial nerve itself. Your own body and its ability to regenerate is the best and only tool that can help the facial nerve recover from injury.

Should I take Prednisolone if there is still no improvement after a few months?

Steroids only work with inflammation or swelling. Thus, taking prednisolone or other steroids within one, two, or more months of the onset of facial neuritis will have no effect. They will not improve your facial nerve’s ability to regenerate. Optimal diet, stress reduction, healthy sleep and an overall healthy lifestyle are the best tools for your recovery.

That is why in the acute phase rest, positive emotions, proper nutrition and avoiding panic and imagining that this is the end of the world are recommended. No, this is not the end. Recovery will come . This may take time. A few weeks or even a few months, but it will definitely happen.

It is important to note that if your recovery takes longer (3-4 months or longer), there is a high chance of residual effects and complications. However, it’s not forever. If you are willing to do something about it, invest your time and effort into consistent work, then these complications can be reduced. This is what we dedicate our work and work to – to return your Smile. Feel free to contact us if you have any questions or would like more information.

Principles of the use of glucocorticoids in the treatment of rheumatic diseases, taking into account their effectiveness and safety

Golovna >

Articles >

Principles of the use of glucocorticoids in the treatment of rheumatic diseases, taking into account their effectiveness and safety

Cycle “Essential drugs WHO”. Methylprednisolone

Authors:
V.N. Kovalenko, O.B. Yaremenko, N.M. Fur coat and others

03/20/2018

Glucocorticoids (GCs) have been widely used in medicine since the middle of the 20th century, after the first successful experience of using cortisol and hydrocortisone for the treatment of patients with rheumatoid arthritis (RA) by a group of American scientists (P.S. Hench, C. Slocumb, H. Polley, 1948). The results were so impressive that the researchers who isolated the first glucocorticoid hormones from the adrenal glands and began to use them for therapeutic purposes were awarded the Nobel Prize two years later (E.C. Kendall, T. Reichsten, P.S. Hench, 1950).

Synthetic HAs such as prednisone, prednisolone, methylprednisolone, betamethasone, dexamethasone and triamcinolone are used in modern rheumatology practice. There is not a single rheumatic disease in which GCs would not be used in certain regimens, although their role and capabilities differ significantly depending on the specific pathology (Table 1).

In systemic connective tissue diseases and vasculitis, GCs are first-line drugs, without which it is impossible to achieve clinical and laboratory remission. In the practice of RA treatment, the relevance of GC remains, despite the introduction of biological disease-modifying drugs, although the issues of dosing and duration of GC therapy in this disease remain the subject of discussion.

Nomenclature and classification of HA
According to the chemical composition, HA are divided into non-fluorinated (prednisone, prednisolone, methylprednisolone) and fluorinated (betamethasone, dexamethasone, triamcinolone, flumethasone, etc.). The presence of fluorine in the molecule reduces the mineralocorticoid properties, but is associated with the risk of developing myopathy. This is the basis for the recommendation to avoid the use of dexamethasone, triamcinolone, and betamethasone in patients with dermatomyositis or known myopathy.

Synthetic HAs are more active than natural hormones and therefore act at lower doses. With a similar direction of action, synthetic HAs are characterized by a different ratio of glucocorticoid and mineralocorticoid properties – respectively, the severity of the anti-inflammatory effect and side effect profiles also differ. Based on these differences, tables of relative effectiveness and equivalent doses of HA were compiled (Tables 2, 3). 5 mg prednisolone corresponds to 4 mg methylprednisolone, 0.75 mg dexamethasone or betamethasone. Mineralocorticoid activity (the ability to retain sodium, cause edema, increase blood pressure) is practically absent in methylprednisolone, dexamethasone and betamethasone, slightly pronounced in prednisolone, and the highest in cortisone and hydrocortisone. In this regard, cortisone and hydrocortisone, which began the therapeutic triumph of HA 70 years ago, are currently used to treat diseases with adrenal hypofunction, and not for anti-inflammatory purposes.

Also, GCs are classified according to the duration of action, which depends on the half-life (Table 2). Cortisone and cortisol are most quickly excreted from the body. Intermediate-acting drugs include prednisolone, methylprednisolone and triamcinolone, while long-acting drugs include dexamethasone and betamethasone. It is not recommended to prescribe GCs with a long half-life for long-term use in order to avoid suppressing the production of one’s own glucocorticoid hormones. Therefore, dexamethasone and betamethasone are mainly used for initial and intensive care. If long-term therapy is necessary, preference is given to prednisolone and methylprednisolone, which are characterized by an optimal balance of anti-inflammatory effect and side effects.

Mechanisms of action
For the rational use of HA, it is necessary to have an idea about the mechanisms of action and their characteristics in different representatives of this group of drugs. To date, it is known that HAs differ in ways of realizing their immunosuppressive and anti-inflammatory potential. There are two pathways of GA action: genomic and non-genomic (F. Buttgereit et al. Ann. Rheum. Dis. 2002; 61 (8): 718-22).

The genomic effects of HA are mediated at doses of ≥2.5 mg prednisolone equivalent via binding to intracellular cytosolic α-receptors (GRα). The therapeutic effect develops no earlier than 30 minutes after the formation of the hormone receptor complex. By binding to GRα, HAs affect intracellular signaling pathways that go from the membrane to the nucleus and mediate the expression of genes for the synthesis of pro-inflammatory factors, and also regulate vital metabolic processes in the cell. GCs stimulate the production of lipocortin, which blocks phospholipase A2. As a result, the breakdown of phospholipids with the formation of arachidonic acid is blocked and, consequently, the synthesis of pro-inflammatory leukotrienes and prostaglandins is disrupted. Blockade of the nuclear transcription factor kappa B (NF-κB) leads to inhibition of the synthesis of interleukins 1 and 6, tumor necrosis factor-α (TNF-α), and metalloproteinases. NF-κB also affects the activity of inducible NO synthase, which is associated with the development of cytotoxic oxidative stress and systemic inflammatory response.

Through complex modulation of cytokines, interleukins and adhesion molecules, as well as interference in the processes of proliferation and protein synthesis, HA block the excessive activation of almost all cellular links of the immune-inflammatory response, including macrophages, monocytes, endothelial cells, basophils, fibroblasts and lymphocytes. Thus, the anti-inflammatory and immunomodulatory effects of HA are realized in several parallel ways at once.

Non-genomic effects of develop within the first seconds and minutes after administration of high doses of HA. They are explained by the direct interaction of HA molecules with biomembranes, as well as steroid-selective membrane receptors.

There are four main groups of non-genomic effects:

1) stabilization of cell membranes and organelle membranes, reduction of capillary endothelial permeability, protection of cells from cytotoxic effects;
2) inhibition of the activity of phagocytic mononuclear cells;
3) suppression of leukocyte migration to the focus of inflammation;
4) decrease in the functional activity of endotheliocytes, monocytes, macrophages, neutrophilic granulocytes and fibroblasts.

Dexamethasone and methylprednisolone have the most pronounced non-genomic effects. They are sold starting from 60 mg in prednisolone equivalent. Therefore, it is these drugs in high doses that are used for pulse therapy in rheumatology.

It should be noted that GCs block the inflammatory cascade at a higher level than non-steroidal anti-inflammatory drugs (NSAIDs) do. If we compare HA with other anti-inflammatory drugs that are used to treat rheumatic diseases (sulfasalazine, gold salts, methotrexate, cyclosporine, antibodies to TNF-α), then the effect of HA on the synthesis of cytokines and other inflammatory factors, as well as the functions of immunocompetent cells is more universal and comprehensive.

The study of the mechanisms of implementation of numerous intracellular effects of HA is ongoing. There is reason to believe that some differences between HAs are due to the peculiarities of their receptor interaction. The existence of two types of glucocorticoid receptors, GRα and GRβ, has been proven, which are expressed in the cytoplasm of almost all body cells. α-receptors are recognized as the main ones in the chain of realization of the effects of GC, while the physiological role of β-receptors has long remained unclear. GRβ are present in smaller amounts and do not bind HA. Some, but not all, studies have found that GRβ has a dominant negative effect on GRα-induced transactivation of GK-dependent genes (C.M.Bamberger et al. J.Clin. Invest. 1995; 95:2435-2441. P.J. Hauk et al. Am. J. Respir. cell. Mol. Biol. 2002; 27:361-367. R.H. Oakley et al. J Biol. Chem. 1999; 274: 27857-27866). In other words, it is likely that GRβ counteracts the realization of the known genomic effects of GA through GRα. In autoimmune inflammatory diseases, GRβ overexpression is possible, which often leads to the development of resistance to GC. That is, the existence of GRβ may explain the therapeutic failures of GC therapy. However, there is evidence that the GRβ response is not the same under the influence of various HAs. According to O.Fruchter et al., GRβ inhibits GRα-induced transactivation stimulated by triamcinolone, dexamethasone, hydrocortisone and betamethasone by 96, 68, 62 and 49%, respectively, but this was not observed with methylprednisolone (O. Fruchter et al. J. Clin. Endocrinol. Metab. 2005; 90: 3505-3509).

The data obtained indicate that methylprednisolone may be the drug of choice in the development of resistance to other GCs.

Pulse Therapy
In 1976 E.S. Cathcart et al. reported a positive effect of infusions of ultra-high doses of methylprednisolone in patients with lupus glomerulonephritis and a rapid deterioration in renal function. From that moment, the formation of the concept of GC pulse therapy began.

Pulse therapy is intermittent administration of drugs in suprapharmacological doses to enhance the therapeutic effect and reduce the risk of side effects. Doses of HA in this case exceed 250 mg / day in prednisolone equivalent for 1-5 days (F. Buttgerent et al. Ann. Rheum. Dis. 2002; 61: 718-722).

For pulse therapy, GCs are used both alone and in combination with cytostatics (most often cyclophosphamide), plasmapheresis, or intravenous immunoglobulin.

Indications for pulse therapy are severe rheumatic diseases and systemic connective tissue diseases with a risk of life-threatening outcomes (rheumatoid vasculitis, severe refractory course of ankylosing spondylitis, lupus nephritis, lesions of the central nervous system, severe vasculitis, dermatomyositis, etc.). In systemic vasculitis, pulse therapy is especially indicated in the early stages of the development of inflammatory changes in the vascular wall, before the onset of irreversible ischemic, necrotic changes in organs and tissues (at the stage of remission induction).

Pulse therapy is contraindicated if the patient has an infectious disease, stomach ulcer, glaucoma, poorly controlled arterial hypertension (AH), decompensated diabetes mellitus (DM). However, all contraindications are relative when it comes to saving lives.

In the implementation of the pronounced therapeutic effect of high doses of HA, an important role is played by rapid non-genomic effects – stabilization of cell membranes and organelle membranes, a decrease in the permeability of capillary endothelium, and protection of cells from cytotoxic effects.

Most often, methylprednisolone is used for pulse therapy of HA in clinical practice, which is characterized by a long-lasting effect (24-72 hours after infusion) and a linear nature of binding to blood plasma proteins (the concentration of methylprednisolone in blood plasma corresponds to the dose of the administered drug). The anti-inflammatory effect of methylprednisolone is superior in severity to that of cortisone, hydrocortisone, prednisolone and prednisone, and the mineralocorticoid effect is practically not manifested.

Depending on the individual characteristics of the patient and the clinical situation, the doctor can use one of the options for GC pulse therapy (V.A. Nasonova, E.L. Nasonov et al., 2012):

– classic – methylprednisolone at a dose of 1000 mg / day intravenously by drip for 3 days in a row;
– medium intensity (“midi”-pulse therapy) – methylprednisolone at a dose of 500 mg / day intravenously by drip for 3 days in a row;
– low intensity (“mini”-pulse therapy) – methylprednisolone at a dose of 250 mg / day intravenously by drip for 3 days in a row.

There are no special indications for mini-, midi- and classic pulse therapy. The regimen is determined on an individual basis, taking into account the severity of the condition, the risk of side effects and contraindications.
To prevent side effects, excessively rapid administration of HA should be avoided and the patient’s condition should be monitored during and after the infusion. Most side effects appear during the administration of the drug or after a few hours, very rarely – on the second or third day. Due to the fact that side effects require rapid correction (for example, hyperglycemia), pulse therapy should be performed only in a hospital setting.

Side effects of HA and safety issues
The interference of synthetic HA, used for therapeutic purposes, in various metabolic pathways of almost all body cells causes a wide range of undesirable effects (Table 4).

In the European League Against Rheumatism (EULAR) recommendations for the use of systemic GCs for the treatment of rheumatic diseases (Ann. Rheum. Dis. 2007; 66: 1560-1567), the frequency of side effects is ranked according to data from randomized controlled trials (Table 5). All side effects of GC are dose-dependent, which can be traced even in the range of low doses – from 5 to 7.5 mg / day in prednisolone equivalent. Some authors identify minimal dangerous doses below which the development of a side effect is unlikely or insignificant (G. Ruiz-Irastorza et al. Rheumatology, 2012 Jul; 51 (7): 1145-53). However, according to other data, there is no lower dose limit for most effects, and, for example, loss of bone mineral density occurs when GC is taken for more than 6 months at any dose (A. Kavanaugh et al. Rheumatology, 2014; 53 (10): 1742-1751 ).

Also, the side effects of HA are classified according to the time of occurrence. For example, osteoporosis, hyperglycemia, and Cushing’s syndrome are observed early, from the first months of treatment, and cataracts are among the delayed cumulative effects of long-term GC use.

In clinical practice, truly dangerous and unacceptable side effects should be distinguished from biases and stereotypes that impair compliance and carry the risk of therapeutic failure. The significance of some side effects tend to be exaggerated and dramatized by both patients and doctors. However, with the advent of more advanced HA molecules (in particular, methylprednisolone) and new research results, a number of myths regarding the side effects of HA have been dispelled. The poor tolerability profile of high doses of HA cannot be automatically transferred to patients taking low doses. In addition, in clinical practice it is sometimes difficult to distinguish side effects from signs of progression or complications of the disease for which they are prescribed.

Thus, the increase in body weight, characteristic of high doses of HA, is minimized when using low doses of modern HA molecules and may be associated not so much with the metabolic effects of HA, but with a decrease in inflammation activity and a decrease in the phenomena of rheumatoid cachexia. Similar weight gain has also been reported in patients receiving TNF-α inhibitors (M.S. Jurgens et al. Arthritis Care Res. 2013; 65 (1): 88-93).

According to Piper et al. GCs are less likely to cause severe gastrointestinal damage than NSAIDs. The two-fold increase in the risk of developing gastric ulcers described during GC treatment may be associated with the combined use of NSAIDs (J. M. Piper et al. Ann. Intern. Med. 1991; 114: 735-740).

Studies have shown a 33% risk of osteoporotic fractures in patients with RA taking HA at an average dose of 8.6 mg/day of prednisone over 5 years. However, the inflammatory activity of RA and the limitation of physical activity of patients with this disease are no less important risk factors for the development of osteoporosis than the osteoresorptive effect of HA (M.C. Van der Goes. Osteop. Int. 2013; 24: 1429-36).

One of the dangerous side effects of HA is hyperglycemia, which can lead to the manifestation of diabetes in people without such a diagnosis or to the failure of compensation in patients with a diagnosis of diabetes who are receiving treatment. However, with careful monitoring of the glycemic profile, this undesirable effect of GC can be successfully compensated by increasing the dose of insulin or oral hypoglycemic drugs.

The question of assessing the ratio of the risk of side effects and the benefits of prescribing GCs for systemic therapy remains relevant and widely discussed. At the EULAR congress in 2016, a promising risk assessment tool was presented – the HA toxicity index (GTI), which is a summed indicator of the action of HA on different organs and systems (E.M. Miloslavsky et al. Ann. Rheum. Dis. 2017; 76 ( 3): 543-546). As a result of information analysis and consensus decision-making, 19 experts from 11 specialties on the use of HA developed and proposed to evaluate the toxicity of HA by 31 indicators. The components of this indicator are estimates of body mass index, glucose tolerance, hypertension, lipid metabolism data, bone mineral density, severity of steroid myopathy, skin changes, neuropsychiatric changes and infections.

Changes in each of these systems with the help of mathematical coefficients are graded as improvement, no change, moderate impairment, severe impairment. It is planned to create an online interface based on the GTI to use this indicator both in clinical trials and in real clinical practice. In the meantime, the development and validation of such a clinical tool continues, expert societies offer a pragmatic approach to the use of HA in rheumatological practice.

Current principles for the use of HA
The EULAR (2007) guidelines for the use of HA in the treatment of rheumatic diseases set out 10 key points that can be briefly summarized as fundamental principles:

– individual selection of the dose of HA depending on the disease, inflammation activity, risk factors, response to treatment;
– minimizing the dose and duration of administration as much as possible;
– accounting for comorbidities and risk factors;
– the appointment of additional therapy to counteract or compensate for the side effects of GC. For example, calcium and vitamin D during GC therapy at doses of ≥7.5 mg/day for prednisolone for more than 3 months.

In 2013, EULAR issued evidence-based and peer-reviewed recommendations for the treatment of rheumatic diseases with medium and high doses of HA (Ann. Rheum. Dis. doi: 10.1136/annrheumdis-2013-203249). Before prescribing medium/high doses of HA, comorbidities and conditions that may increase the risk of side effects of HA, such as diabetes, impaired glucose tolerance, cardiovascular disease, peptic ulcer, recurrent infections, immunosuppression, glaucoma, and osteoporosis, should be evaluated. In this case, additional factors should be taken into account: for example, a healthy diet and physical activity in cardiovascular diseases are preventive factors and reduce the overall risk, while the long course of the disease, poorly controlled hypertension and dyslipidemia increase the risk.

An adequate starting dose of HA should be selected to achieve the desired therapeutic response, taking into account the risk of treatment failure. In the future, the need to continue taking GCs and dose adjustment should be constantly reviewed depending on the therapeutic response and side effects.

Conclusions
Based on the EULAR recommendations for HA therapy in patients with rheumatic diseases, in order to ensure safer use of HA in everyday clinical practice, it is reasonable to perform the following steps.

1. The patient should be informed about the possible side effects of GC therapy before starting it.
2. The choice of the starting dose of the drug, as well as subsequent tactics for long-term GC therapy, is carried out taking into account the type of rheumatic disease, the activity of the pathological process, the presence of risk factors and the characteristics of the patient’s individual response to treatment; timing of GC intake may be important due to the circadian rhythm of adrenal cortex activation.
3. When considering the advisability of prescribing HA, the presence of comorbidities and risk factors for adverse reactions, as well as the need for therapeutic interventions to prevent them, should be taken into account.
4. With long-term GC therapy, doses of drugs should be minimal, and in the case of remission or low disease activity, it is advisable to reduce the dose.
5. Depending on the individual risk of the patient, the dose and duration of GC intake during treatment, monitoring of body weight, hypertension, intraocular pressure, blood lipid and glucose levels, the presence of edema, the development of symptoms of heart failure should be carried out. The new GC Toxicity Index (GTI) can be used to assess side effects of GC therapy.
6. Initial therapy with prednisone at a dose of ≥7.5 mg/day and treatment duration of more than 3 months should be given calcium and vitamin D supplements. Bisphosphonate antiresorptive therapy to prevent GC-induced osteoporosis should be based on an assessment of risk factors, including data from the study of bone mineral density.
7. Patients receiving GCs and non-selective NSAIDs should be given gastroprotective therapy or alternative treatment with selective cyclooxygenase-2 inhibitors. It should be emphasized that studies on the evaluation of gastroprotective measures in patients who take GCs have not been conducted, therefore, today it is important in the prevention of gastrointestinal complications with the simultaneous use of GCs and NSAIDs is the use of the safest means, in particular methylprednisolone.
8. All patients who received GC therapy for more than 1 month, if there are indications for surgical intervention, should be given adequate replacement therapy to compensate for possible adrenal insufficiency.
9. GC use during pregnancy is not associated with additional risk to mother and child (dose should not exceed 10 mg/day of prednisone). The drugs of choice for patients in this category are methylprednisolone and prednisolone. These drugs are intensively metabolized in the placenta, entering the fetal blood in small concentrations (10% of the dose), while the concentration of dexamethasone in the fetal blood can be quite high, and therefore its use is appropriate if it is necessary to stimulate the maturation of the lungs in the fetus and with confidence that the expected benefit to the mother outweighs the possible risk to the fetus.
10. Growth should be assessed regularly in children taking GCs and, if growth is delayed, growth hormone replacement therapy should be instituted.

At the present stage, the use of HA remains an important direction in the treatment of rheumatic diseases, which require timely identification of risk factors and careful monitoring of the condition of patients during treatment, as well as strict adherence to recommendations regarding the rational use of these drugs. These activities will improve the safety of long-term GC therapy, increase the duration and improve the quality of life of patients with rheumatic diseases.

PDF article

Thematic issue “Cardiology, Rheumatology, Cardiosurgery” No. 1 (56) February 2018

• Current topic:
• WHO Essential Medicines series. Methylprednisolone

• Number:
• Thematic issue “Cardiology, Rheumatology, Cardiosurgery” No.