Doxorubicin is a chemotherapy drug that is given as a treatment for many different cancers. It used to be called Adriamycin and some doctors and nurses still use this name. This information describes doxorubicin, how it is given and some of its possible side effects.

What Doxorubicin looks like

Doxorubicin is a red fluid.

How it is given

Doxorubicin is given:

• by injection into a vein (intravenously) through a fine tube (cannula) placed into the vein in your arm
• through a central line (Hickman / Portacath), which is inserted under the skin into a vein near the collarbone, or into a PICC line which is inserted into a vein in the crook of your arm.
• Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated.

Possible side effects

Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given doxorubicin, and may be different if you are having more than one chemotherapy drug.

We have outlined the most common side effects and some of the less common ones, so that you can be aware of them if they occur. However, we have not included those which are very rare and therefore extremely unlikely to affect you. If you do notice any effects which you think may be due to the drug, but which are not listed in this information, please discuss them with your doctor or chemotherapy nurse.

Hair loss

Usually starts 3–4 weeks after the first dose of doxorubicin, although it may happen earlier. All your hair may fall out. You may also have thinning and loss of eyelashes, eyebrows and other body hair. Hair loss is temporary and all your hair will regrow once the treatment ends. To help reduce hair loss, scalp cooling may be suitable for some people.

Feeling sick (nausea) and being sick (vomiting)

If you do feel sick this may begin a few hours after the treatment is given and last for up to a day. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective.

Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.

Lowered resistance to infection

Doxorubicin can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given, and your resistance to infection usually reaches its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily, and will usually have returned to normal levels before your next course of chemotherapy is due.

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy, to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.

Bruising or bleeding

Doxorubicin can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, or bleeding gums. Your platelet count will be checked before each treatment.

Anaemia (low number of red blood cells)

While having treatment with doxorubicin you may become anaemic. This may make you feel pale, tired and short of breath on exertion. You may need to have a transfusion of blood if the number of red blood cells becomes too low.

Sore mouth and ulcers

Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.

Taste changes

You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.

Discoloured urine

Your urine may become a pink-red colour. This may last up to 48 hours after you have had the doxorubicin, and is due to the colour of the drug. It is quite normal.

Skin changes

Your skin may darken, due to excess production of pigment. This usually returns to normal a few months after the treatment has finished.

Sensitivity to the sun

While you are having doxorubicin, and for several months afterwards, you will be more sensitive to the sun, and your skin may burn more easily. You can still go out in the sun, but you should wear a high protection factor suncream and protective clothing and a hat.

Tiredness and feeling weak

You may feel very tired. It is important to allow yourself plenty of time to rest.

Less common side effects

Changes in the way your heart works

Higher doses of doxorubicin may cause changes in the muscle of the heart. This can affect how the heart works. The effect on the heart depends on the dose given. It is very unusual for the heart to be affected if you receive standard doses. Tests to see how well your heart is working (such as an echocardiogram or MUGA scan) may sometimes be carried out before the drug is given.

Diarrhoea

This can usually be easily controlled with medicines such as loperamide or codeine, but tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea.

Skin changes

The skin may become red and sore in areas which have previously been treated with radiotherapy. Let your doctor know if this happens. The skin over the vein used for the injection may become discoloured.

Changes in nails

Your nails may become darker. White lines may appear on them. These changes usually grow out over a few months once treatment has finished.

Additional information

Some people have hot flushes when this drug is being given.

Leakage into the tissue

If doxorubicin leaks into the tissue around the vein it can cause damage. If you notice any stinging or burning around the vein while the drug is being given, or any leakage of fluid from the cannula site it is very important that you tell your nurse or doctor.

If the area around the injection site becomes red or swollen at any time you should either tell the doctor or nurse on the ward, or, if you are at home, ring the clinic or ward and ask to speak to the doctor or nurse.

Risk of blood clots

Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood. Your doctor or nurse can give you more information.

Other medicines

Some medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility

Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.

Contraception

It is not advisable to become pregnant or father a child while taking doxorubicin, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.

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Additional Information For Healthcare Professionals

‘ADVERSE REACTIONS SIGNIFICANT

• Cardiovascular: Acute cardiotoxicity: Atrioventricular block, bradycardia, bundle branch block, ECG abnormalities, extrasystoles (atrial or ventricular), sinus tachycardia, ST-T wave changes, supraventricular tachycardia, tachyarrhythmia, ventricular tachycardia
• Delayed cardiotoxicity: LVEF decreased, CHF (manifestations include ascites, cardiomegaly, dyspnea, edema, gallop rhythm, hepatomegaly, oliguria, pleural effusion, pulmonary edema, tachycardia); myocarditis, pericarditis
• Central nervous system: Malaise
• Dermatologic: Alopecia, itching, photosensitivity, radiation recall, rash; discoloration of saliva, sweat, or tears
• Endocrine & metabolic: Amenorrhea, dehydration, infertility (may be temporary), hyperuricemia
• Gastrointestinal: Abdominal pain, anorexia, colon necrosis, diarrhea, GI ulceration, mucositis, nausea, vomiting
• Genitourinary: Discoloration of urine
• Hematologic: Leukopenia/neutropenia (75%; nadir: 10-14 days; recovery: by day 21); thrombocytopenia and anemia
• Local: Skin “flare” at injection site, urticaria
• Neuromuscular & skeletal: Weakness
• Postmarketing and/or case reports: Anaphylaxis, azoospermia, bilirubin increased, chills, coma (when in combination with cisplatin or vincristine), conjunctivitis, fever, gonadal impairment (children), growth failure (prepubertal), hepatitis, hyperpigmentation (nail, skin & oral mucosa), infection, keratitis, lacrimation, myelodysplastic syndrome, neutropenic fever, oligospermia, onycholysis, peripheral neurotoxicity (with intra-arterial doxorubicin), phlebosclerosis, radiation recall pneumonitis (children), secondary acute myelogenous leukemia, seizure (when in combination with cisplatin or vincristine), sepsis, shock, systemic hypersensitivity (including urticaria, pruritus, angioedema, dysphagia, and dyspnea), transaminases increased, urticaria

MECHANISM OF ACTION

Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.

PHARMACODYNAMICS / KINETICS

• Absorption: Oral: Poor (<50%)
• Distribution: Vd: 809-1214 L/m2; to many body tissues, particularly liver, spleen, kidney, lung, heart; does not distribute into the CNS; crosses placenta
• Protein binding, plasma: 70% to 76%
• Metabolism: Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides
• Half-life elimination:
  • Distribution: 5-10 minutes
  • Elimination: Doxorubicin: 1-3 hours; Metabolites: 3-3.5 hours
  • Terminal: 17-48 hours
  • Male: 54 hours; Female: 35 hours
  • Excretion: Faeces (~40% to 50% as unchanged drug); urine (~5% to 12% as unchanged drug and metabolites)
  • Clearance: Male: 113 L/hour; Female: 44 L/hour