bleomycin
Appearance:Clear, colourless solution
; may be mixed into larger bags of fluids
Monograph Name:bleomycin
Monograph Body:
Bleomycin is an antibiotic complex produced by fermentation from Streptomyces verticillus. It causes single- and double-strand DNA breaks through formation of an intermediate iron complex. DNA synthesis, and to a lesser degree, RNA and protein synthesis are inhibited. Bleomycin is cell cycle phase-specific.
Oral: no
Well absorbed after parenteral (IV, Subcut, IM) administration. About 45% of the dose is absorbed into the circulation after intrapleural administration. Absorption from subcut is delayed and may resemble a slow IV infusion.
Rapid distribution to tissues. High concentrations in skin, lung, kidney, peritoneum and lymphatics.
Low concentrations are found in the bone marrow.
Cross blood brain barrier? | no |
PPB |
Limited |
Inactivated by hydrolases in many tissues. The liver and GI tract show the highest rate of inactivation, while skin, lungs and kidneys show a lower rate.
Squamous cells are highly sensitive to bleomycin due to their low bleomycin hydrolase content.
Active metabolites |
yes |
Inactive metabolites | yes |
Excreted by kidneys; terminal half-life increases exponentially as creatinine clearance falls. Elimination during the first 24 hours is lower after most intracavitary administrations than after IV administration.
Urine |
66% unchanged |
Half-life |
2-5 hours (IV bolus) |
- Squamous cell cancer - head and neck, skin, penis, cervix and vulva
- Hodgkin and Non-Hodgkin lymphoma (including lymphosarcoma and reticulum cell sarcoma)
- Testicular cancer
- Malignant pleural effusion
The response is poorer in patients with head and neck cancer who have received previous radiotherapy.
Other Uses:
- Germ Cell Cancers
Emetogenic Potential:
Extravasation Potential: None
ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
---|---|---|---|---|---|
Cardiovascular | Arterial thromboembolism (rare) | E | |||
Hypotension (rare) | I | ||||
Other - Pleuropericarditis (rare) | E | ||||
Venous thromboembolism (<10%) | E | ||||
Dermatological | Alopecia (30%) (partial) | E | |||
Nail disorder (11%) | E D | ||||
Other - Hyperkeratosis (≤ 50%; hands, nails) | E D | ||||
Radiation recall reaction (rare) | I | ||||
Rash , pruritis (8%; skin folds, friction areas) | E | ||||
Skin hyperpigmentation (41%) skin folds, nail cuticles, friction areas, IM injection sites | E D | ||||
Gastrointestinal | Anorexia, weight loss (29%) | E | |||
Mucositis (30%) | E | ||||
Nausea, vomiting (15%) | I | ||||
General | Fatigue (16%) | E | |||
Fever, chills (50%) (50% with IV; 25% with IM) | I | ||||
Tumour pain (rare) | E | ||||
Hematological | Hemolytic uremic syndrome (rare) | E | |||
Hepatobiliary | ↑ LFTs (rare) | E | |||
Hypersensitivity | Anaphylaxis (<10%) (lymphoma patients 1%) | I | |||
Injection site | Phlebitis (rare) | I E | |||
Renal | Creatinine increased (rare) | E | |||
Respiratory | Pneumonitis (10%) (1% fatal) | D | |||
Vascular | Peripheral ischemia (Raynaud's; with vinblastine) | E |
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for bleomycin include fever/chills, skin hyperpigmentation, hyperkeratosis, alopecia (partial), mucositis, anorexia, fatigue, nausea/vomiting, nail disorder, and pneumonitis.
Skin and mucosal changes are the most frequent side effects, occurring in approximately 50% of treated patients and include stomatitis, alopecia, hyperpigmentation, ulceration, erythema, hyperkeratosis, nail changes, rash, vesiculation, tenderness, pruritus, peeling, striae and bleeding. Hypoesthesia may occur at the onset of skin toxicity, and may progress to hyperesthesia. Adverse mucocutaneous effects usually develop in the 2nd or 3rd week of bleomycin treatment. These appear to be dose-related and are usually observed after 150-200 units of bleomycin have been administered. Discontinuation of bleomycin due to these toxicities has occurred in 2% of patients. Bleomycin can cause unusual pigmentation on the trunk consisting of linear streaks with crisscross patterns in 8-22% of patients.
Fever and chills occur in approximately 50% of patients. These reactions usually occur starting a few hours after treatment, and may last up to 4-12 hours. Acetaminophen q3-4h prn can be used to control fever if it occurs. Anaphylaxis is reported in 1% of patients with lymphoma after the 1st or 2nd dose; it may be immediate or delayed for several hours.
Bleomycin lung toxicity occurs in 10% of patients and is fatal in 1%. Changes in pulmonary functions tests occur in 20% of patients receiving bleomycin. Dyspnea and fine rales are early symptoms of pulmonary toxicity. The clinical symptoms, radiologic and microscopic findings are not specific to bleomycin lung toxicity. The incidence of pulmonary toxicity increases significantly at a cumulative dose of >400 U. Risk factors include age >70 years, pre-existing pulmonary disease, coexisting renal failure, prior or concomitant thoracic radiation therapy, subsequent high-dose oxygen exposure (e.g. during anesthesia), smoking or previous exposure to bleomycin within 6 months. Bolus dosing increases the risk of pulmonary toxicity. It has also been observed occasionally in young patients receiving low doses.
Bleomycin therapy should be withheld if the pulmonary diffusion capacity for carbon monoxide (DLCO) falls to 30-35% of initial value, if the forced vital capacity (FVC) falls significantly, or if there are any clinical or radiographic features indicating pulmonary toxicity. Pneumonitis due to bleomycin should be treated with corticosteroids in an effort to prevent progression to fibrosis. Appropriate antibiotic therapy should be given for infectious pneumonitis. Patients should be warned that uncontrolled oxygen should be avoided except briefly in an emergency and to avoid increased oxygen pressure as in scuba diving.
Bleomycin has the potential to enhance radiation injury to tissues. While often called radiation recall reactions, the timing of the radiation may be before, concurrent with or even after the administration of bleomycin. Recurrent injury to a previously radiated site may occur weeks to months following radiation.
Refer to protocol by which patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Maximum lifetime doses should not exceed 400 units (or 200 units/m2; less for patients with lung function or renal impairment), due to increased pulmonary toxicity risk. Not to exceed 100 units/m2 in patients with prior or concurrent lung radiation and in patients over 70 years. For intrapleural administration, consider the absorption in determining the cumulative dose (45% absorbed).
Toxicity Grade / Counts x 109/L |
Action / % previous dose
|
Pulmonary: Pneumonitis; DLCO ≤ 35% of baseline; Rapid ↓in FVC |
Discontinue and investigate. If confirmed treat with corticosteroids.
|
Cardiac : ECG changes; pleuropericarditis |
Hold and investigate; consider ↓ infusion rate or discontinue. |
Grade 3 (related organ) |
Hold until ≤ grade 2, then 75% |
Grade 4 (related organ) |
Discontinue |
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Grade | Management | Re-challenge |
1 or 2 |
Restart:
|
|
3 or 4 |
|
No adjustment required.
Creatinine clearance (mL/min) |
% usual dose |
10 – 50 |
75% |
< 10 |
50% |
Refer to protocols being used.
IM, SC:
- Reconstitute in 1-5mL sterile water or normal saline for injection (concentration 3 to 15 units/mL)
IV:
- Reconstitute with 5-10mL Normal Saline.
- May be given by direct IV push over 10 minutes, followed by a Saline flush, if no IV line has been set up.
- Or may further dilute in 50-100mL Normal Saline (0.3 to 3 units/mL) and infuse over 10-15 minutes.
Intrapleural:
- Dissolve drug in 50 to 100 mL Normal Saline
- Instill via an indwelling thoracostomy tube after drainage. Refer to local guidelines for administration procedures.
- Store unopened vial between 2-8⁰C. Do not freeze.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
- Patients who have demonstrated hypersensitivity to the drug or to its excipients
- Caution should be exercised when used concomitantly with nephrotoxic drugs as they may reduce bleomycin clearance.
- Bleomycin should be used with extreme caution in patients with pre-existing renal or pulmonary disease, and in patients over the age of 70. Patients should avoid high FIO2 for at least a year after completion (i.e. during anesthesia).
Other Drug Properties:
-
Carcinogenicity:
Yes
-
Mutagenicity:
Yes
-
Teratogenicity:
Yes
-
Pregnancy:
Bleomycin is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during bleomycin treatment and for at least 6 months after the last dose. (general recommendation)
-
Excretion into breast milk:
Unknown
Breastfeeding is not recommended during treatment.
-
Fertility effects:
Probable
Bleomycin treatment may cause irreversible infertility.
AGENT | EFFECT | MECHANISM | MANAGEMENT |
---|---|---|---|
Cisplatin or other nephrotoxins | ↓ clearance of bleomycin in patients treated previously or concurrently with cisplatin | cisplatin-induced decrease in GFR | monitor for excessive bleomycin toxicity, especially pulmonary |
Drugs that may cause pulmonary toxicity (e.g. BCNU, mitomycin, cyclophosphamide, methotrexate, gemcitabine) | ↑ risk of pulmonary toxicity with concurrent bleomycin use | additive | monitor for pulmonary toxicity |
digoxin | ↓ effect of digoxin | ↓ absorption of digoxin | monitor |
phenytoin | ↓ efficacy of phenytoin | ↓ absorption of phenytoin | monitor phenytoin serum levels; adjust phenytoin dose if required. |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Monitor Type | Monitor Frequency |
---|---|
Liver function tests (if failure suspected) |
Baseline and as clinically indicated |
Renal function tests |
Baseline and before each cycle |
Clinical assessment of mucocutaneous or respiratory effects, infusion-related reactions, thromboembolism |
At each visit; continue to monitor for pulmonary toxicity for approximately 2 months after treatment completion |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Monitor Type | Monitor Frequency |
---|---|
Pulmonary tests, including DLCO, if patient has pre-existing pulmonary dysfunction, or has had prior pulmonary radiation, if age >70, or if total cumulative Bleomycin dose >400 mg |
Baseline, regular (i.e. monthly) and as clinically indicated |
Cancer Drug Manual (the Manual), 1994, British Columbia Cancer Agency (BCCA)
Bleomycin: e-Drugdex, Micromedex Healthcare Series.
Chen YB, Rahemtullah A, Breeden E, et al. Bleomycin-induced flagellate erythema. J Clin Oncol 2007; 25(7): 898-900.
de Almeida AL, Fortuna A, Sousa M, Sá R. A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility. Reprod Toxicol. 2024 Sep 24;130:108721.
Diao DY, Goodall J. Bleomycin-induced-flagellate dermatitis. CMAJ 2012;184(11):1280.
Compendium of Pharmaceuticals and Specialties. 2006. Blenoxane ®. Canadian Pharmacists Association.
Koberda M, Zieske PA, Raghavan NV, et al. Stability of bleomycin sulfate reconstituted in 5% dextrose injection or 0.9% sodium chloride injection stored in glass vials or polyvinyl chloride containers. Am J Hosp Pharm. 1990 Nov;47(11):2528-9.
Lambertini, M. et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology, Volume 31, Issue 12, 1664 – 1678.
Product Monograph: Bleomycin for Injection. Pfizer Canada Inc. August 8, 2017.
Product Monograph: Bleomycin for Injection. Fresenius Kabi Canada Ltd., June 1, 2016.
Sebti SM and Lazo JS. Metabolic inactivation of bleomycin analogs by bleomycin hydrolase. Pharmac Ther 1988; 38: 321-9.
Stelzer KJ , Griffin TW, Koh WJ, et al. Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome. Cancer. 1993 Feb 15;71(4):1322-5.
Summary of Product Characteristics: Bleomycin. Accord Healthcare Limited (UK). November 2018.
November 2024 Updated Pregnancy and Lactation section
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.
Cancer Drug Manual (the Manual), 1994, British Columbia Cancer Agency (BCCA)
Bleomycin: e-Drugdex, Micromedex Healthcare Series.
Chen YB, Rahemtullah A, Breeden E, et al. Bleomycin-induced flagellate erythema. J Clin Oncol 2007; 25(7): 898-900.
de Almeida AL, Fortuna A, Sousa M, Sá R. A systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility. Reprod Toxicol. 2024 Sep 24;130:108721.
Diao DY, Goodall J. Bleomycin-induced-flagellate dermatitis. CMAJ 2012;184(11):1280.
Compendium of Pharmaceuticals and Specialties. 2006. Blenoxane ®. Canadian Pharmacists Association.
Koberda M, Zieske PA, Raghavan NV, et al. Stability of bleomycin sulfate reconstituted in 5% dextrose injection or 0.9% sodium chloride injection stored in glass vials or polyvinyl chloride containers. Am J Hosp Pharm. 1990 Nov;47(11):2528-9.
Lambertini, M. et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology, Volume 31, Issue 12, 1664 – 1678.
Product Monograph: Bleomycin for Injection. Pfizer Canada Inc. August 8, 2017.
Product Monograph: Bleomycin for Injection. Fresenius Kabi Canada Ltd., June 1, 2016.
Sebti SM and Lazo JS. Metabolic inactivation of bleomycin analogs by bleomycin hydrolase. Pharmac Ther 1988; 38: 321-9.
Stelzer KJ , Griffin TW, Koh WJ, et al. Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome. Cancer. 1993 Feb 15;71(4):1322-5.
Summary of Product Characteristics: Bleomycin. Accord Healthcare Limited (UK). November 2018.
bleomycin (patient)
Info Sheet Introduction:- In combination with other drugs for treating many different types of cancer, such as germ cell, lymphomas
; may be mixed into larger bags of fluids
- In combination with other drugs for treating many different types of cancer, such as germ cell, lymphomas
- Tell your health care team if you have or had:
- kidney or liver disease
- lung disease, or if you smoke
- radiation therapy to the chest
- any allergies
- or if you had bleomycin before and had severe side effects
Remember to:
- Tell your health care team about all of the other medications you are taking.
- Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.
Talk to your health care team about:
- How this medication may affect your sexual health.
- How this medication may affect your ability to have a baby, if this applies to you.
This medication may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.
- If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time until 6 months after your last dose. Talk to your health care team about which birth control options are best for you.
- Do not breastfeed while on this medication.
- This drug is given through an IV (injected into a vein). Talk to your health care team about your treatment schedule.
- If you missed your treatment appointment, talk to your health care team to find out what to do.
-
Will this medication interact with other medications or natural health products?
-
This medication can interact with other medications, vitamins, foods and natural health products. Interactions can make the treatment not work as well or cause severe side effects.
-
Tell your health care team about all of your:
-
prescription and over-the-counter (non-prescription) medications and all other drugs, such as marijuana (medical or recreational)
-
natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements
-
-
Check with your health care team before starting or stopping any of them.
-
-
What should I do if I feel unwell, have pain, a headache or a fever?
-
Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol) or ibuprofen (Advil)).
-
Fever can be a sign of infection that may need treatment right away.
-
If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.
-
How to check for fever:
Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).
- You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
OR
- 38.0°C (100.4°F) or higher for at least one hour.
- 38.3°C (100.9°F) or higher at any time
If you do have a fever:- Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
- Ask your health care team for the Fever pamphlet for more information.
If you do not have a fever but have mild symptoms such as headache or mild pain:
-
Ask your health care team about the right medication for you. Acetaminophen (Tylenol®) is a safe choice for most people.
-
Talk to your health care team before you start taking Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or ASA (Aspirin®), as they may increase your chance of bleeding or interact with your cancer treatment.
-
Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.
-
What to DO while on this medication:
- DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.
What NOT to DO while on this medication:
- DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.
The following table lists side effects that you may have when getting bleomycin. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.
Read over the side effect table so that you know what to look for and when to get help. Refer to this table if you experience any side effects while on bleomycin.
Common Side Effects (26 to 50 out of 100 people) | |
Side effects and what to do | When to contact health care team |
Darkening or thickening of skin; What to look for?
The rash may be seen in areas where you have had radiation before.
Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away. |
Talk to your health care team if no improvement or if severe |
Fever, Flu-like symptoms You may feel like you have the flu for around 2 days after your IV treatment. These flu-like symptoms may not be signs of an infection. What to look for?
What to do?
|
Talk to your health care team if no improvement or if severe |
Hair thinning or loss (generally mild) What to look for?
What to do?
|
Talk to your health care team if this bothers you |
Mouth sores What to look for?
To help prevent mouth sores:
Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information. |
Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow |
Low appetite, weight loss What to look for?
Ask your health care team for the Loss of Appetite pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Less Common Side Effects (10 to 25 out of 100 people) | |
Side effects and what to do | When to contact health care team |
Fatigue What to look for?
What to do?
Ask your health care team for the Fatigue pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Nausea and vomiting (usually mild) What to look for?
To help prevent nausea:
|
Talk to your health care team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if severe |
Nail changes What to look for?
|
Talk to your health care team if it does not improve or if it is severe |
Cough and feeling short of breath (may be severe) What to look for?
Rarely this may be severe with chest pain, trouble breathing or coughing up blood.
|
Talk to your health care team. If you are not able to talk to your health care team for advice, and you have a fever or severe symptoms, you MUST get emergency medical help right away |
Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:
- trouble seeing, speaking, or using your arms and legs
- any new pain in your belly or arms
- pain, swelling and hardening of the vein in an arm or leg
- itchiness, rash, swollen lips, face or tongue, chest and throat tightness, usually during or shortly after the medication was given
- pain, burning, redness, or swelling of your skin where the medication was injected
- yellowish skin or eyes, unusually dark (or red-brown) pee
- feeling unusually tired, bruising easily
- peeing less than usual, new pain in your lower back, swelling in your hands, ankles, feet or other areas of your body
- weight gain that is not normal for you
Who do I contact if I have questions or need help?My cancer health care provider is: ______________________________________________ During the day I should contact:________________________________________________ Evenings, weekends and holidays:______________________________________________
|
Other Notes:
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
____________________________________________________________________________
For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.
The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.
A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.



blee-oh-MY-sin
Cancer Type: Genitourinary Testis Gynecologic Germ Cell Hematologic Lymphoma - Hodgkin Lymphoma - Non-Hodgkin's High Grade Lymphoma - Non-Hodgkin's Intermediate Grade Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Wednesday, November 20, 2024 Universal Date: 2024-11-20 00:00:00 AddThis: Title URL: bleomycin Drug Display Status: Active Revision Summary:Drug Monograph: Updated Pregnancy and Lactation section