Contraceptives and Hormonal Birth Control

Contraception

• Combined Oral Contraceptives (COCs) contain estrogen and progestin, preventing pregnancy (93% effective), acne, and premenstrual dysphoric disorder.
• Off-label uses of COCs include treatment of hirsutism, headaches, premenstrual syndrome, iron deficiency anemia, and cramps.
• Beyaz is a COC specifically used to treat premenstrual dysphoric disorder.

Estrogen

• Estrogen types include ethinyl estradiol, estradiol valerate, and mestranol.
• Estrogen's effects on the body include:
  • Pituitary feedback: inhibiting FSH and ovulation
  • Increasing aldosterone and sodium and water retention
  • Increasing sex hormone binding globulin, which can lead to acne and hirsutism
• Adverse effects of estrogen include:
  • Nausea
  • Cyclic weight gain
  • Bloating/edema
  • Cyclic headaches
  • Hypertension
  • Breast tenderness/fullness

Progestin

• Progestin types include norethindrone, ethynodiol diacetate, noregestrel, desogestrel, and drospirenone.
• Progestin's effects on the body include:
  • Pituitary feedback: inhibiting ovulation
  • Endometrial atrophy and thickening of cervical mucus to prevent sperm travel
• Adverse effects of progestin include:
  • Hair loss
  • Hirsutism
  • Acne
  • Oily skin
  • Libido changes

WHO Contraindications for COCs

• Breakthrough bleeding: adhere to the prescription for 3 months and switch based on when bleeding occurs.
• Nausea: likely related to estrogen; suggest taking it before bed or with food.
• Acne: likely related to progestin/androgens; select a higher estrogen or lower progestin.
• Serious adverse effects: ask the patient about ACHES.
• Drug-drug interactions: anticoagulants, antibiotics, and smoking.

Urge Incontinence / Overactive Bladder

• Anti-muscarinic/cholinergic medications: oxybutynin, tospium, and darifenacin.
• B3 agonist: mirabegron.
• Botox: onabotulinumtoxin A.

Stress Incontinence

• Alpha-adrenergic agonists: pseudoephedrine and phenylephrine.
• Topical estrogen: cream, insert, or ring.
• SNRI: duloxetine (not FDA approved).

Heart Failure

• Diuretics: empagliflozin and dapagliflozin.
• ACEI/ARBs: ACEI has cough, hyperkalemia, uricemia, and angioedema.
• Digoxin: associated with sickle cell, sudden onset myelosuppression, and increased liver function tests.

DNA Cross-Linking Drugs

• Ciclophosphamide: has a broad spectrum, used in rheumatoid arthritis, and SLE.
• Ifosfamide: used in sarcoma, has a high risk of hemorrhagic cystitis.
• Platinum drugs: cisplatin, carboplatin, and oxaliplatin, used in various types of cancer.

Other DNA Alkylating Agents

• Dacarbazine: used in IV Hodgkin's lymphoma and melanoma.
• Busulfan: used in CML, has a high risk of dose-limiting myelosuppression.
• Mitomycin: used in salvage therapy with vincristine, end-stage breast cancer, and bladder cancer.

DNA Intercalating Drugs

• Anthracyclines: doxorubicin, daunorubicin, and idarubicin, used in various types of cancer.
• Dactinomycin: used in Ewing's sarcoma and childhood cancer.

Mitotic Inhibitors

• Taxanes: paclitaxel, docetaxel, and ixabepilone, used in various types of cancer.

• Vinca alkaloids: vinblastine, vincristine, and vinorelbine, used in various types of cancer.

• Topoisomerase inhibitors: teniposide, irinotecan, and topotecan, used in various types of cancer.### Chemotherapy

• Etoposide: PO palliative chemotherapy, requires large volume of fluids, often used with cisplatin for lung cancer, and in BMT/refractory disease, phosphate salt form requires less fluid.

• Diarrhea: common side effect of etoposide, can be managed with loperamide.

Targeted Anticancer Drugs

• Tyrosine Kinase Inhibitors (TKIs): most successful, impede pathways promoting malignant cell transformation and proliferation, common side effects: rash, diarrhea, and mucositis.
• Common Toxicities with TKI Target:
  • EGFR: rash, diarrhea, mucositis
  • HER2: rash, diarrhea, left ventricular dysfunction
  • VEGF: hypertension, proteinuria, prolonged wound healing, VTE risk
  • BCR-ABL: cytopenia, hypothyroidism

Tyrosine Kinase Inhibitors

• Imatinib (1st line): inhibits TK expressed by Philadelphia chromosome, used in CML, GI stroma, side effects: rash, diarrhea
• Dasatinib:
• Nilotinib:
• Erlotinib: epidermal growth inhibitor, used in 2nd line NSCLC, side effects: skin rash, diarrhea, mucositis
• Bortezomib: used in multiple myeloma, side effects:

Monoclonal Antibodies

• Often used as adjuvant to chemotherapy regimens, side effects: Stevens-Johnson syndrome, anaphylaxis, infusion reactions
• Infusion reactions: can be managed with acetaminophen, diphenhydramine, and methylprednisolone 30 minutes before infusion
• Highest risk of infusion reactions: -mab, -xiab, -zumab, lowest risk: -mab, -umab

Monoclonal Antibodies (continued)

• Rituximab: used in non-Hodgkin's lymphoma, SLE, RA, ITP, can cause tumor lysis syndrome
• Alemtuzumab: used in CLL after alkylating, side effects:
• Gemtuzumab: used in CD33 (+) AML, side effects:
• Glucarpidase: used to treat toxic [c] levels due to renal dysfunction

Diarrhea Management

• Loperamide: used to manage irinotecan-induced diarrhea, and fluorouracil-induced diarrhea, may require steroids, and atropine.