DOXORUBICIN (doxorubicin hydrochloride) 8 USE IN SPECIFIC POPULATIONS

(doxorubicin hydrochloride)

Prescribing Information

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) the recommended human dose of 60 mg/m2 (see Data). Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Doxorubicin hydrochloride was teratogenic and embryotoxic at doses of 0.8 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) when administered during the period of organogenesis in rats. Teratogenicity and embryotoxicity were also seen using discrete periods of treatment. The most susceptible was the 6- to 9-day gestation period at doses of 1.25 mg/kg/day and greater. Characteristic malformations included esophageal and intestinal atresia, tracheo-esophageal fistula, hypoplasia of the urinary bladder, and cardiovascular anomalies. Doxorubicin hydrochloride was embryotoxic (increase in embryo‑fetal deaths) and abortifacient at 0.4 mg/kg/day (about 0.07 times the recommended human dose based on body surface area) in rabbits when administered during the period of organogenesis.

8.2 Lactation

Risk Summary

Doxorubicin was measured in the milk of one lactating patient after therapy with 70 mg/m2 of doxorubicin hydrochloride given as a 15-minute intravenous infusion. The peak milk concentration at 24 hours after treatment was 4.4-fold greater than the corresponding plasma concentration. Doxorubicin was detectable in the milk up to 72 hours. There are no data on the effects of doxorubicin hydrochloride on the breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with Doxorubicin Hydrochloride Injection and for 10 days after the final dose.

8.3 Females and Males of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating Doxorubicin Hydrochloride Injection.

Contraception

Females

Doxorubicin Hydrochloride Injection can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use highly effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 6 months after treatment. [see Use in Specific Populations (8.1)].

Males

Doxorubicin hydrochloride may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Due to the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection and for 3 months after treatment [see Nonclinical Toxicology (13.1)]. Males with pregnant partners should use condoms during treatment and for at least 10 days after the final dose [see Nonclinical Toxicology (13.1), Use in Specific Populations (8.1)].

Infertility

Females

In females of reproductive potential, Doxorubicin hydrochloride may cause infertility and result in amenorrhea. Premature menopause can occur. Recovery of menses and ovulation is related to age at treatment [see Nonclinical Toxicology (13.1)].

Males

Doxorubicin hydrochloride may result in oligospermia, azoospermia, and permanent loss of fertility. Sperm counts have been reported to return to normal levels in some men. This may occur several years after the end of therapy [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

Based on postmarketing reports, pediatric patients treated with doxorubicin hydrochloride are at risk for developing late cardiovascular dysfunction. Risk factors include young age at treatment (especially < 5 years), high cumulative doses and receipt of combined modality therapy. Long-term periodic cardiovascular monitoring is recommended for all pediatric patients who have received doxorubicin hydrochloride. Doxorubicin hydrochloride, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary.

There are no recommended dose adjustments based on age. Doxorubicin clearance was increased in patients aged 2 years to 20 years as compared to adults, while doxorubicin clearance was similar in infants less than 2 years as compared to adults [see Clinical Pharmacology (12.3)].

8.5 Geriatric Use

Clinical experience in patients who were 65 years of age and older who received doxorubicin hydrochloride-based chemotherapy regimens for metastatic breast cancer showed no overall differences in safety and effectiveness compared with younger patients.

8.6 Hepatic Impairment

The clearance of doxorubicin was reduced in patients with elevated serum total bilirubin levels. Doxorubicin Hydrochloride Injection is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin levels greater than 5 mg/dL) [see Contraindications (4)]. Reduce the dose of Doxorubicin Hydrochloride Injection in patients with serum total bilirubin levels greater than 1.2 mg/dL [See Dosage and Administration (2.4), Warnings and Precautions (5.5)].

Medication Guide

MEDICATION GUIDE

Patient Information
DOXORUBICIN (dok-suh-roo-buh-sin) HYDROCHLORIDE injection, for intravenous use
What is the most important information I should know about Doxorubicin?
Doxorubicin may cause serious side effects including: • Heart muscle problems. Doxorubicin can cause heart muscle damage that may lead to heart failure. Heart failure means your heart does not pump blood well. Heart failure is irreversible in some cases and can lead to death. Heart failure can happen during your treatment with Doxorubicin or months to years after stopping treatment. Your risk of heart muscle damage increases with higher total amounts of Doxorubicin that you receive in your lifetime. Your risk of heart failure is higher if you: o have other heart problems o have had or are currently receiving radiation therapy to your chest o have had treatment with certain other anti-cancer medicines o take other medicines that can have severe side effects on your heart Tell your healthcare provider if you get any of these symptoms of heart failure during or after treatment with Doxorubicin:
	o extreme tiredness or weakness o shortness of breath	o fast heartbeat o swelling of your feet and ankles
	Your healthcare provider will do tests to check the strength of your heart muscle before, during, and after your treatment with Doxorubicin.
• Heart rhythm problems. Doxorubicin can cause serious heart rhythm problems that may lead to death. This can happen during your infusion, within a few hours after your infusion or anytime during treatment with Doxorubicin. Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast, irregular or slow, or you feel lightheaded, dizzy, short of breath, chest discomfort or you faint. • Risk of new cancers. You may have an increased risk of developing certain blood cancers called acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after treatment with Doxorubicin. Talk with your healthcare provider about your risk of developing new cancers if you receive Doxorubicin. • Skin damage at or near the vein where Doxorubicin is given. Doxorubicin can damage the skin if it leaks out of the vein and might cause blisters, skin sores or severe tissue damage, which may require skin grafts. Tell your healthcare provider if you get burning or stinging during your infusion. • Decreased blood cell counts. Doxorubicin can cause a decrease in neutrophils (a type of white blood cell important in fighting bacterial infections) and platelets (important for clotting and to control bleeding). This may lead to a serious infection, the need for blood transfusions, treatment in a hospital or death. Your healthcare provider will check your blood cell counts before each infusion and during treatment with Doxorubicin. Call your healthcare provider right away if you get a fever (temperature of 100.4°F or higher) or chills with shivering.
What is Doxorubicin?
Doxorubicin is a prescription medicine used to treat certain types of cancers. Doxorubicin may be used alone or along with other anti-cancer medicines.
Do not receive Doxorubicin if: • you have had a recent heart attack (within the past 4 to 6 weeks) or have severe heart problems. • your blood cell counts (platelets, red blood cells, and white blood cells) are very low because of prior chemotherapy. • you have severe liver problems. • you have had a severe allergic reaction to Doxorubicin.
Before you receive Doxorubicin, tell your healthcare provider about all of your medical conditions, including if you: • have heart problems including heart failure. • are currently receiving radiation therapy or plan to receive radiation to the chest. • have liver problems. • have had an allergic reaction to doxorubicin. • are pregnant or plan to become pregnant. Doxorubicin can harm your unborn baby. You should not become pregnant during treatment with Doxorubicin. Tell your healthcare provider right away if you become pregnant or think you may be pregnant. Females who are able to become pregnant: o Your healthcare provider will check to see if you are pregnant before you start treatment with Doxorubicin. o You should use effective birth control (contraception) during treatment with Doxorubicin and for 6 months after treatment. Males: o Doxorubicin can affect your sperm and could cause birth defects. o If you have a female partner who can become pregnant, you should use effective birth control during treatment with Doxorubicin and for 3 months after treatment. o If you have a pregnant partner, you should use condoms during treatment with Doxorubicin and for at least 10 days after the final dose. o Talk to your healthcare provider about birth control methods that may be right for you. • are breastfeeding or plan to breastfeed. Doxorubicin can pass into your breast milk. Do not breastfeed during treatment with Doxorubicin and for 10 days after the final dose. Talk to your healthcare provider about the best way to feed your baby during this time.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive Doxorubicin? • Doxorubicin will be given to you into your vein through an intravenous (IV) line. • Your healthcare provider will do blood tests to check for side effects during treatment with Doxorubicin. • Your healthcare provider may stop your treatment, change the timing of your treatment, or change the dose of your treatment if you have certain side effects while receiving Doxorubicin.
What are the possible side effects of Doxorubicin?
Doxorubicin may cause serious side effects, including: • See “What is the most important information I should know about Doxorubicin?”
The most common side effects of Doxorubicin include: • total hair loss (alopecia). Your hair may re-grow after your treatment. • nausea • vomiting
Other side effects: • Red colored urine. You may have red colored urine for 1 to 2 days after your infusion of Doxorubicin. This is normal. Tell your healthcare provider if it does not stop in a few days, or if you see what looks like blood or blood clots in your urine. • Call your healthcare provider if you have severe symptoms that prevent you from eating or drinking, such as: o nausea o vomiting o diarrhea o mouth pain or sores
Doxorubicin may cause fertility problems in males. This could affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.
Doxorubicin may cause fertility problems in females. Your periods (menstrual cycle) may completely stop when you receive Doxorubicin. Your periods may or may not return following treatment. Early menopause has also happened. Talk to your healthcare provider if this is a concern for you.
These are not all of the possible side effects of Doxorubicin.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of Doxorubicin.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.
You can ask your pharmacist or healthcare provider for information about Doxorubicin that is written for health professionals.
What are the ingredients in Doxorubicin?
Active ingredient: doxorubicin hydrochloride
Inactive ingredients for Doxorubicin Hydrochloride Injection: sodium chloride, and hydrochloric acid, USP.

LAB-0436-5.0
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This Patient Information has been approved by the U.S. Food and Drug Administration.			Revised: 7/2024

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