Denosumab (Subcutaneous)

Denosumab is a drug belonging to the class of medications known as monoclonal antibodies.

Overview

Denosumab is a drug which is administered subcutaneously in order to treat osteoporosis (bone loss). It is usually given to post-menopausal women who are considered at high risk of bone fractures due to osteoporosis, and older men who are also more likely to suffer from broken bones.

Osteoporosis is a condition which can cause the bones to thin and to become more brittle and more easily susceptible to fractures and breaks. Osteoporosis can run in families, so you are more likely to be at risk of the condition if a relation has suffered from osteoporosis. The chances of developing this condition also increase with age and if the patient has been taking corticosteroids for a long period of time.

It is also used as a precautionary measure for women who are being given various medications to treat breast cancer. Some of these forms of medication leave the patients at higher risk of osteoporosis whilst undergoing the treatment. The same is true for men receiving prostate cancer treatment.

Denosumab is a medication which belongs to a group of drugs known as monoclonal antibodies. This class of drugs target particular proteins which are either produced by certain cells or which are attached to the surface of individual cells.

Denosumab is used to slow the bone loss, meaning that bones stay stronger for longer and this reduces the chances of fractures. In healthy bones, there are two types of cell which work together in order to maintain the bone and to rebuild and strengthen any weaknesses. Osteoclasts break down the old bone and osteoblasts then rebuild the new bones in a process of regeneration. When cancer is present with the bone, these cells start to behave in different ways. Osteoclasts begin to work too hard, breaking down too much bone and leaving the patient with thinner bones which are more susceptible to fractures.

Denosumab tackles this problem by targeting a particular protein which the osteoclasts rely on in order to reproduce and function. By binding itself to these proteins, Denosumab stops them from being able to work with the osteoclasts, so the osteoclasts are unable to reproduce and break down the bone matter. This slows down the degeneration of the bones by osteoporosis and helps maintain healthier bones for longer.

Conditions treated

Type of medicine

  • monoclonal antibodies

Side Effects

If doctors prescribe their patients with a certain type of medication, they will be doing so because they consider the benefits of the medication to outweigh the risk of possible side effects. Most people who are given Denosumab to treat or prevent osteoporosis do not experience severe side effects.

The most common side effect of taking Denosumab is reduced calcium levels. This is particularly common in patients who are already suffering from kidney problems. It is, however, possible to treat this side effect separately to the osteoporosis. Doctors will often prescribe both calcium and vitamin D supplements to patients taking Denosumab in order to restore calcium levels to normal during treatment. It is common for patients to have their blood calcium levels tested before the first injection of Denosumab is administered and repeatedly during treatment. Symptoms of low calcium levels include:

  • Muscle cramps
  • Spasms
  • Changes in mood
  • Numbness or tingling in the extremities
  • Irregular heartbeat
  • Confusion
  • Seizures
  • Dizziness, and in extreme cases, fainting

All of the symptoms listed above are associated with low calcium levels, which can be corrected quickly and easily by taking calcium supplements. If you experience any of these symptoms, you should seek medical attention and make sure that the doctor is aware that you have been receiving Denosumab treatment. They may tell you to take calcium supplements to offset the effect of the drug on calcium levels, to change your diet or to increase your daily dose of calcium if you are already taking it.

Another common side effect of Denosumab is a diminished immune system. Whilst being treated with Denosumab, patients are at risk of a weakened immune system as the drug an also affect the proteins associated with different forms of antibodies. Patients taking Denosumab can have a higher chance of developing a serious infection if their immune system is unable to fight off harmful bacteria and other pathogens. This could develop anywhere in the body, but is most likely to occur in the ear, stomach, bladder or skin. Common symptoms of serious infection include:

  •  Ear pain
  • Unusual discharge
  •  Painful urination
  •  Increased frequency of urination
  •  Difficult hearing
  •  Fever
  •  Swelling and redness
  •  Presence of pus
  •  Severe abdominal cramps

Any of the symptoms listed above could be a sign of a serious infection which would require urgent medical attention. Let your doctor know straight away if you suspect you have an infection after having received Denosumab treatment, as your immune system may be less able to cope than it normally would.

Other side effects of Denosumab can include:

  •  Jaw pain
  •  Muscle pain
  •  New pain in the joints, especially in the hips and groin
  •  Skin problems e.g. blisters, zits, itching, peeling, redness

It is very unusual for patients to be seriously allergic to Denosumab, however it is possible. If you experience any of the following symptoms, seek immediate medical attention and make sure that the medical staff are aware that you have received Denosumab treatment:

  •  Rashes
  •  Difficulty reading
  •  Swelling
  •  Itching
  •  Hives
  •  Swollen face
  •  Dizziness and confusion

If you notice a worsening of any condition whilst taking Denosumab, or any negative changes in your physical or mental health since you started taking Denosumab, make sure to let your doctor or healthcare professional know straight away, as they will be able to decide the best course of action going forward.

Dosage

Denosumab is administered to patients via an injection which is inserted subcutaneously into the upper arm, stomach or thigh. There are two different types of Denosumab: Xgeva and Prolia. Xgeva is normally given to the patient every 4 months, whereas Prolia is usually administered every 6 months.

The dose of Denosumab given can vary according to:

  •  The condition being treated
  •  The age of the patient
  •  Other medical conditions which the patient is also suffering from

Patients should make sure to attend all appointments so that no doses are skipped. If a dose is missed for whatever reason, the patient should reschedule an appointment as quickly as possible for the dose to be administered.

Interactions

When a patient is being treated for multiple conditions at the same time, there is always a chance that when combined, the medications for different illnesses may begin to work differently. These differences in the behavior of the medication or pharmaceuticals is known as an interaction. Interactions can occur whenever a patient is taking more than one form of medication, drug or dietary supplement at once. Interactions can affect the body in different ways, either by causing the medication to be less effective, increasing the possibility of existing side effects or causing a new condition, not previously suffered by the patient.

There are few known interactions between Denosumab and other drugs.

Etelcalcetide (also known as Parsabiv) is not recommended for use with Denosumab as both of these drugs can lower the levels of calcium in the blood. As this is a side effect which can be countered by the consumption of additional calcium supplements, it may be that your doctor is happy to continue to prescribe both types of medication, provided that the calcium levels can be kept under control. Similarly, patients who already suffer from a calcium deficiency may be advised to take extra care whilst on a course of Denosumab.

Immunosuppressants are also known to interact with Denosumab. Denosumab can lower a patient's immune system and leave them open to infection and disease. When the immune system is not operating properly, it becomes much harder for the body to fight off harmful pathogens and bacteria. Taking more than one drug known to have this effect at the same time can greatly increase the risk to the patient.

Warnings

It is sometimes possible for drugs to have unintended reactions to underlying medical conditions which the patient may be suffering at the same time as receiving their treatment for a different illness or condition. It is therefore extremely important to keep an up-to-date and comprehensive medical history and record of all medications being taken, to avoid any interactions between drugs and different conditions. When undergoing a course of Denosumab, it is especially important for patients to let their doctor know if any of the statements below are true:

  •  You have ever experienced an allergic reaction to Denosumab
  •  You are allergic to any medications that you are aware of
  •  You have a latex allergy
  •  You have ever suffered from a calcium deficiency or low calcium levels
  •  You have, or have ever had, an overactive or underactive thyroid
  •  You have recently have, or plan to soon have, a tooth extraction procedure
  •  You have a stomach or intestinal condition
  •  You suffer from kidney failure or any kidney problems
  •  You are pregnant, or plan to become pregnant whilst having this treatment
  •  You are breastfeeding, or plan to breastfeed whilst having this treatment

Denosumab is not recommended as a treatment for children. The nature of the drug can inhibit growth and development and also affect the way in which the teeth are formed and maintained.

Denosumab is thought to harm unborn babies and is therefore not to be used by pregnant mothers. The use of reliable forms of contraception can be discussed with your doctor in order to prevent pregnancy whilst undergoing this treatment. It is extremely important to let your doctor know if you are pregnant or plan to become pregnant whilst taking the drug.

It is not known whether the use of Denosumab in prospective fathers can harm a baby if the father is taking the drug at the time of conception.

There is a possibility of issues with the jawbone as a consequence of osteoporosis. It is therefore important to keep your dentist updated on your condition and treatment as it may affect any dental work which you need to have done. Whilst undergoing treatment for osteoporosis, it is more important than usual not to miss dental appointments and to receive regular dental checkups in order to maintain healthy teeth and gums and to avoid the need for major dental procedures. If you begin to experience any jaw pain whilst receiving Denosumab, let your doctor and/or dentist know immediately.

Storage

Denosumab is not normally administered outside of medical institutions, and it is therefore straightforward to keep the drug in a controlled environment. Denosumab should be refrigerated but not frozen and kept at a steady temperature between 2°C - 8°C. The vials should remain in their original opaque outer packaging in order to protect the drug from being damaged by exposure to light.

Vials of the drug should be clearly labelled so that they cannot be mistaken for other forms of medication and administered incorrectly. As with all medications, Denosumab should be stored somewhere safe where it cannot be confused with other substances or forms of medication. It should be kept out of the way of pets and children.

As Denosumab is administered subcutaneously via an injection, needles and syringes will be required in order to treat the patient with this medication. Once used, all needles should be carefully disposed of using a sharps bin, which should be collected and emptied by qualified staff members. The needles should be kept separately to the vials.

Summary

Denosumab is a drug used to prevent the deterioration of bones in patients who have, or are at high risk of developing, osteoporosis.

It is a form of monoclonal antibody, which works by preventing the parts of the cell responsible for breaking down damaged bone from being able to function as quickly. This slows down the degeneration of bone matter and helps patients with osteoporosis to retain healthier bones for much longer.

There are two main types of Denosumab: Xgeva and Prolia. There are few differences between the function of these drugs, but one is administered every 4 weeks and the other only has be injected once every six months.

Denosumab does not usually cause adverse side effects in patients who take it regularly. It can, however, cause calcium levels in the body to drop rapidly, which can lead to a calcium deficiency. Low calcium levels can cause side effects. The drug can also lead to a lowered immune system which leaves the body less well-protected against infection. Patients can therefore develop infections and diseases more quickly and easily if not careful.

Denosumab is a treatment, not a cure, and its effects are not long-lasting after treatment. Patients are much more susceptible to brittle and easily-broken bones soon after they stop receiving the treatment.