Daratumumab (Intravenous)

As a monoclonal antibody, Daratumumab is effective in the treatment of various cancers including multiple myeloma, large B cell lymphoma, mantle cell lymphoma and follicular lymphoma.

Overview:

Since 2015, Daratumumab has been approved for the treatment of various forms of cancer in patients who have received at least three prior types of therapy, which can include proteasome inhibitors, immunomodulatory agents or immunomodulatory agents 'making it a suitable treatment for patients who have relapsed. It is administered intravenously, and can be used in conjunction with other medicines (including dexamethasone and/or pomalidomide) to treat multiple myeloma.

Daratumumab, which is often marketed as Darzalex, is a monoclonal antibody which works in several separate ways. It attaches itself to multiple myeloma cells within the body and kills them directly. It can also attach to these cells and allow the immune system to destroy them. It targets a protein known as CD38, which is present at the surface of many different cell types (including red blood cells).

When combined with other medications, Daratumumab has a high success rate. As many as eight out of 10 patients who undergo treatment with this medicine experience positive results within one month of therapy.

Type of medicine:

  • Monoclonal antibody

Conditions treated:

  • Multiple myeloma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Diffuse large B cell lymphoma

Side effects:

Along with the desired effects, Daratumumab can also cause some unwanted side effects. The most commonly reported side effects by patients undergoing treatment with this medicine include the following: dizziness, blurred vision, fevers, chills, facial swelling, voice, headache, ear congestion, chest pain or tightness, nausea, shortness of breath, pounding in the ears, slow or fast heartbeat, sore throat, sneezing, difficulty breathing, nervousness, back pain, diarrhea, constipation, joint pain, appetite loss, muscle stiffness and/or pain in the arms or legs.

As the patient continues to receive treatment with Daratumumab, most (if not all) of the previously mentioned side effects should lessen. If side effects continue for a prolonged period or appear to worsen, the patient is advised to contact their doctor as soon as possible. In some instances, a healthcare provider may be able to offer advice on how to alleviate side effects which are causing mild discomfort via the use of over the counter or natural remedies.

Most patients generally only experience minimal side effects when undergoing treatment with Daratumumab, if they experience any whatsoever. Most healthcare professionals agree that the benefits of undergoing treatment with this medicine far outweigh the risks of experiencing mild or moderate side effects.

Other side effects, which are experienced less frequently (although often enough to warrant mentioning) include the following: confusion, light-headedness (especially when standing up quickly from a prone position), painful blisters on the trunk of the body, skin rash, hives, sweating, unusual weakness or tiredness, pain when urinating, sore throat, ulcers on the skin, unusual bruising or bleeding, pinpoint red spots, lower back or side pain, bleeding gums and/or black and tarry stools.

Because Daratumumab can affect the psychology of the patient (confusion and light-headedness), patients are advised to avoid driving or operating heavy machinery until it has been observed that the patient does not experience these side effects and is therefore competent enough to perform tasks which require coordination and concentration. This is so the patient avoids inadvertently injuring themselves or another party due to being unfit because of Daratumumab use.

Not all side effects may have been reported, and patients may experience side effects which are not currently listed. In the event of this happening, the patient is advised to contact their doctor and to report any findings to the FDA.

Dosage:

As with all medicines, it is imperative that the patient is administered with Daratumumab only as directed by a qualified physician. This means that healthcare professionals should avoid administering more of this medicine than advised, both in terms of frequency of use as well as dose size. In addition to this, the patient should stop taking this medication if a doctor advises so, even if a supply of Daratumumab remains.

Usual adult dosage for multiple myeloma:

When used as a monotherapy, or in conjunction with dexamethasone or lenalidomide, the following dosage regimen should be adhered to:

  • Weeks 1 to 8: 16mg/kg intravenous solution, once a week.
  • Weeks 9 to 24: 16mg/kg intravenous solution, once every two weeks.
  • ¬†Weeks 25 and beyond: 16mg/kg every four weeks until the disease is sufficiently under control.

When used as a combination therapy in conjunction with dexamethasone or bortezomib, the following dosage regimen should be adhered to:

  • Weeks 1 to 9: 16mg/kg intravenous solution, once a week (total of 9 doses).
  • Weeks 10 to 24: 16mg/kg intravenous solution, once every three weeks (total of 5 doses).
  • ¬†Weeks 25 and beyond: 16mg/kg every four weeks until the disease is sufficiently under control.

Before therapy with Daratumumab begins, the patient should be administered with pre-and post-infusion medicines which can include corticosteroids, antipyretics and antihistamines.

Infusion rates for Daratumumab:

For the first infusion of this medication, healthcare professionals should administer at a dilution rate of 1000ml, with 50ml of Daratumumab received by the patient in the initial hour. This can be increased in increments of 50ml per hour up to a maximum of 200ml/hour.

For the second infusion of this medication, healthcare professionals should administer at a dilution rate of 500ml, with 50ml of Daratumumab received by the patient in the initial hour. This can be increased in increments of 50ml per hour up to a maximum of 200ml/hour.

For subsequent infusions of this medication after the second, healthcare professionals should administer at a dilution rate of 500ml, with 50ml of Daratumumab received by the patient in the initial hour. This can be increased at increments of 50ml per hour up to a maximum of 200ml/hour.

An increase in infusion levels should only be considered in patients who do not face any infusion-related reactions to the drug. A decreased dilution rate should also only be considered in the event that the patient experiences no infusion-related reactions (or mild reactions only) during the first three hours of administration.

Although the manufacturers of this medication provide general dosing information, it should be reiterated that these are mere recommendations which can be altered at the discretion of a doctor. When determining the optimal dose, a doctor will take into account the height, weight, age and condition of a patient among other criteria.

There are no recommended dose sizes for children. Instead, the manufacturer leaves it up to the doctor overseeing treatment to determine the optimum pedatric dose.

In the event of missing a dose, patients are advised against being treated with a double dose to make up for the missed dose, as this can increase the potential for an overdose to occur. Patients who experience signs of overdose (shallow breathing, fast or slow heartbeat, pale or bluish appearance in color, loss of consciousness) are advised to contact their local poison control center immediately on 1800-222-1222 or the emergency services on 911. Alternatively, patients can make their way to the local ER if it is in close enough proximity.

Interactions:

All drugs can potentially interact with other substances, chemicals or medications within the human body. In some instances, an interaction can cause one or more medicines to become ineffective in treating a condition. In other instances, interactions can cause potentially dangerous or even fatal side effects. Because of these risks, patients are advised to keep full and detailed lists of all medicines they are currently being treated with. This extends to herbal supplements, vitamins, over the counter remedies and complementary medicines as well as prescription medications.

The following is a partial list of medicines known to interact with Daratumumab. Patients who are taking one or more of these medicines should consult their doctor or healthcare provider prior to undergoing their first treatment with Daratumumab:

  • Adalimumab
  • BCG
  • Certolizumab
  • Clozapine
  • Deferiprone
  • Etanercept
  • Fingolimod
  • Golimumab
  • Infliximab
  • Influenza Virus Vaccine, H1N1, Live
  • Influenza Virus Vaccine, Live, Trivalent
  • Leflunomide
  • Measles Virus Vaccine
  • Measles Virus Vaccine/Mumps Virus Vaccine/Rubella Virus Vaccine
  • Mumps Virus Vaccine
  • Mumps Virus Vaccine/Rubella Virus Vaccine
  • Natalizumab
  • Poliovirus Vaccine, Live, Trivalent
  • Alemtuzumab
  • Anakinra
  • Anthrax Vaccine Adsorbed
  • Azathioprine
  • Canakinumab
  • Candida Albicans Extract
  • Cholera Vaccine
  • Cholera Vaccine, Live
  • Cladribine
  • Coccidioidin Skin Test
  • Denosumab
  • Diphtheria And Tetanus Toxoids/Pertussis, Acellular
  • Diphtheria Toxoid/Haemophilus B Conjugate (Hboc) Vaccine/Pertussis, Whole Cell/Tetanus Toxoid
  • Efalizumab
  • Filgrastim
  • Ganciclovir
  • Haemophilus B Conjugate (Hboc) Vaccine
  • Haemophilus B Conjugate (Prp-Omp) Vaccine
  • Haemophilus B Conjugate (Prp-Omp) Vaccine/Hepatitis B Pediatric Vaccine
  • Haemophilus B Conjugate (Prp-T) Vaccine
  • Haemophilus B Conjugate (Prp-T) Vaccine/Meningococcal Conjugate Vaccine
  • Hepatitis A Adult Vaccine
  • Hepatitis A Adult Vaccine/Hepatitis B Adult Vaccine
  • Hepatitis A Pediatric Vaccine
  • Ocrelizumab
  • Olaparib
  • Omacetaxine
  • Pegfilgrastim
  • Plague Vaccine
  • Pneumococcal 13-Valent Vaccine
  • Pneumococcal 23-Polyvalent Vaccine

Warnings:

Patients who have ever had an allergic reaction to this or any other medication should inform their doctor, as they may not be suitable for treatment with Daratumumab. This is because it may contain active or inactive ingredients which are known allergens in some patients.

If a patient has ever had a breathing disorder or a history of herpes zoster (also known as shingles), this treatment may not be suitable for them.

Using Daratumumab when pregnant is not advised, as it could potentially harm unborn fetuses. Patients who are pregnant or intending on becoming pregnant should not use this medicine. Patients who use this medicine are advised to use effective birth control, such as condoms, to prevent pregnancy for the duration of treatment with this medicine, and for at least three months after the last dose of Daratumumab.

Storage:

Daratumumab is typically administered by qualified healthcare professionals in a clinical setting, who will be aware of storage guidelines. It should be kept refrigerated (between 2C and 8C) and kept in its original packaging to protect it from light.

Summary:

While Daratumumab is greatly beneficial in the treatment of patients with multiple myeloma, there are also risks associated with this medicine. It is therefore imperative that patients are upfront regarding their medical history (including allergies) prior to receiving treatment with this medicine.

When used correctly, Daratumumab helps patients to overcome cancer, providing them with a greater quality of life. In order to achieve this, patient and doctor must work together to find out the most suitable dose.