Sexual & Reproductive Health PDF

Sexual & Reproductive Health Table 8. Bisphosphonates (Cont’d) Drug Indications Ibandronate (Boniva) Prevention and treatment of osteoporosis in women Zoledronic acid (Reclast) Osteoporosis Dosing and Routes 150 mg PO monthly 3 mg IV every 3 mo Not recommended for CrCl < 30 mL/min Prevention...

Sexual & Reproductive Health Table 8. Bisphosphonates (Cont’d) Drug Indications Ibandronate (Boniva) Prevention and treatment of osteoporosis in women Zoledronic acid (Reclast) Osteoporosis Dosing and Routes 150 mg PO monthly 3 mg IV every 3 mo Not recommended for CrCl < 30 mL/min Prevention and treatment of 5 mg IV yearly osteoporosis in postmenopausal women, 5 mg IV every 2 yr (prevention in women) increase BMD in men, glucocorticoidNot recommended for CrCl < 35 mL/min induced osteoporosis Paget disease BMD = bone mineral density; CrCl = creatinine clearance; IV = intravenously; PO = by mouth. 2. Denosumab (Prolia): Approved for postmenopausal women with osteoporosis at high risk of fracture, for increasing bone mass in men with osteoporosis, for treatment of glucocorticoid-induced osteoporosis, and for men and women with bone loss associated with prostate or breast cancer. a. Inhibits osteoclast-mediated bone resorption; monoclonal antibody against receptor activator of nuclear factor қ β ligand (RANKL) (cytokine essential for formation, function, survival of osteoclasts) b. Considered alternative first-line therapy. i. Patients at high risk of fracture or intolerant of or unresponsive to bisphosphonates ii. Patients with impaired renal function c. Administered as 60 mg subcutaneously every 6 months d. Not contraindicated with renal dysfunction. e. Efficacy i. Increased hip (6%) and spine (9%) BMD ii. Reduced spinal fracture risk by 68%, hip fracture risk by 40% iii. Optimal duration is not well studied. Length of therapy guided by clinical judgment and re-evaluation of fracture risk. f. Safety issues i. Possible opportunistic infections, skin infections such as cellulitis ii. Hypocalcemia: Patients should take calcium and vitamin D together with denosumab. Those with impaired renal function are more likely to have hypocalcemia. iii. The FDA has Risk Evaluation and Mitigation Strategies (REMS) requirements for this drug (Medication Guide). iv. Administration of a bisphosphonate after denosumab discontinuation has been proposed as a strategy to mitigate a transient rebound of bone turnover causing rapid BMD loss and increased risk of multiple vertebral fractures (Osteoporos Int 2016;27:1677-82). 3. Calcium a. Recommended for all patients to maintain normal calcium concentrations and to prevent hypocalcemia associated with other drug treatments for osteoporosis b. Elemental calcium intake: Avoid doses higher than 2500 mg/day. Higher doses may increase risk of constipation, contribute to kidney stones, and inhibit absorption of zinc or iron (Table 9). c. Most common forms: Calcium carbonate (take with food), calcium citrate (take with or without food, may be good option for patients taking antacids or acid-suppressive therapy or for patients with achlorhydria) d. Systematic reviews and meta-analyses have raised concerns about the potential association between calcium supplements and an increased risk of cardiovascular disease (Nutrients 2021;13:368). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-566 Sexual & Reproductive Health Table 9. Recommended Daily Calcium Intake Age Group 19–50 yr: Women 51–70 yr: Men ≥ 51 yr: Women ≥ 71 yr: Men Recommended Daily Calcium Intake (mg) 1000 1200 4. Vitamin D a. Recommended for all patients; promotes calcium reabsorption. b. Minimum dose is 800 international units/day for those older than 70 years, 600 international units/ day age 70 years and younger. c. Higher doses of vitamin D may be necessary for those with vitamin D concentrations less than 30 ng/mL. d. Goal: 30 ng/mL in adults, although concentrations of 20 ng/mL may be adequate for most of the population. 5. Selective estrogen receptor modulators a. Raloxifene (Evista) i. Indication: Prevention and treatment of osteoporosis in postmenopausal women. Risk reduction for invasive breast cancer in postmenopausal women ii. Preferred agent in this class because of long-term safety/efficacy data and reduced risk of breast cancer iii. Mechanism: Selective estrogen receptor modulator (a) Reduction in resorption of bone. (b) Decrease in overall bone turnover. (c) Data suggest estrogen antagonist in uterine and breast tissue. (d) Consider use for primary prevention in women with low BMD and a 5-year risk of developing invasive breast cancer greater than 3% (Ann Intern Med 2013;158:604). iv. Efficacy (a) Reduces the risk of vertebral fractures (30%–50%); has not been shown to decrease hip fractures. (b) Lowers total cholesterol by 7% and LDL by 11%; does not reduce risk of CHD. v. Adverse reactions (a) Hot flashes: 6%–25% (b) Leg cramps: 6% (c) VTE: About 1% (2- to 3-fold increased risk compared with placebo) vi. Dose: 60 mg/day orally vii. Contraindications (a) Pregnancy, nursing, pediatrics (b) History of VTE events; greatest risk of VTE events occurs during first 4 months. viii. Drug interactions (a) Bile acid resins decrease absorption by 60%. (b) Warfarin: Prothrombin time is decreased by 10%. (c) Thyroid hormones: Separate administration by 12 hours. b. Conjugated estrogens and bazedoxifene (Duavee) i. Indication: Prevention of osteoporosis in postmenopausal women ii. Few long-term safety data. Considered alternative agent to prevent bone loss in patients with a uterus and persistent menopausal symptoms who cannot tolerate other drugs. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-567 Sexual & Reproductive Health iii. Mechanism: Selective estrogen receptor modulator plus estrogen (tissue-selective estrogen complex [TSEC]) iv. Efficacy (a) Significantly increased total hip BMD at 24 months by 1.96% compared with placebo in women who had been postmenopausal for 1–5 years and by 1.73% in women who had been postmenopausal for more than 5 years. (b) Significantly increased mean lumbar spine BMD (by 1.51%) compared with placebo at 12 months in women who had been postmenopausal for 1–5 years. v. Adverse reactions (5% or more) (a) Hot flashes (b) Muscle cramps (c) Throat, neck, and muscle pain (d) Dizziness (e) Nausea and vomiting vi. Dose: Conjugated estrogen 0.45 mg and bazedoxifene 20 mg/day orally vii. Contraindications (a) Pregnancy, nursing, pediatrics (b) History of VTE events or coagulopathy (c) Hepatic impairment (d) Similar to estrogen contraindications viii. Drug interactions: Metabolized by cytochrome P450 (CYP) 3A4; inducers or inhibitors of CYP3A4 may affect estrogen concentrations. 6. Human parathyroid hormone related peptide analogs a. Teriparatide (Forteo) i. Recombinant human parathyroid hormone regulates bone metabolism, intestinal calcium absorption, and renal tubular calcium and phosphate reabsorption. ii. Indications: Treatment of postmenopausal women with osteoporosis that have a high risk of fracture, increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture iii. Efficacy (a) Reserved for treating women at high risk of fracture, including those with very low BMD (T-score lower than –3.0) and a previous vertebral fracture. (b) Decreases vertebral fractures by 65% and non-vertebral fractures by 53%; not shown to decrease hip fractures. iv. Contraindications: Hypercalcemia, bone metastases, disorders that predispose women to bone tumors such as Paget disease, and alkaline phosphatase elevation (unexplained) v. Adverse effects: Nausea, orthostatic hypotension vi. Carcinogenicity: Osteosarcoma in rats; should not be used longer than 2 years. vii. Drug interactions: Increases calcium concentrations and may increase risk of digoxin toxicity. viii. Dosage: 20 mcg/day subcutaneously b. Abaloparatide (Tymlos) i. Regulates bone metabolism, intestinal calcium absorption, and renal tubular calcium and phosphate reabsorption. ii. Indication: Treatment of postmenopausal women with osteoporosis that have a high risk of fracture. iii. Efficacy (a) Reserved for treating women at high risk of fracture, including those with very low BMD (T-score lower than –3.0) and a previous vertebral fracture. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-568 Sexual & Reproductive Health (b) Decreases vertebral fractures by 86% and non-vertebral fractures 43%; not shown to decrease hip fractures. iv. Contraindications: None v. Precautions (1) Orthostatic hypotension; (2) Hyperkalemia; (3) Hypercalciuria and urolithiasis: vi. Adverse effects: Nausea, dizziness, headache, palpitations, hypercalciuria, upper abdominal pain, and vertigo vii. Carcinogenicity: Osteosarcoma in rats; should not be used longer than 2 years. viii. Drug interactions: Increases calcium concentration and may increase risk of digoxin toxicity. ix. Dosage: 80 mcg/day subcutaneously; patients should also take supplemental calcium and vitamin D if dietary intake is not enough. 7. Romosozumab-aqqg (Evenity) a. Sclerostin (a factor in bone regulation) inhibitor, helps build bone and decreases bone resorption. b. Indication: Treatment of osteoporosis in postmenopausal women who are at high risk of fracture (defined as a history of osteoporotic fracture or several risk factors for fracture) or for those whose other osteoporosis treatments have failed c. Efficacy: Decreased the absolute risk of new vertebral fracture by 1.3% at 12 months (fracture risk in placebo group 1.8% vs. 0.5% in treatment group, p<=0.001) and by 1.9% at 24 months (fracture risk in placebo group 2.5% vs. 0.6% in treatment group, p=<0.001); increased BMD by 12.7% at lumbar spine, 5.8% at total hip, 5.2% at femoral neck d. Contraindications: Hypocalcemia, sensitivity to romosozumab e. Precautions: Major adverse cardiac events (MI, stroke); hypocalcemia; hypersensitivity (e.g., allergic reaction, angioedema); osteonecrosis of the jaw and atypical femoral fracture i. Should not be initiated in patients who have had an MI or stroke within the previous year. ii. Consider risk-benefit of therapy in patients with other CV risk factors. f. Adverse effects: Joint pain and headache g. Carcinogenicity: None reported h. Dosages: 210 mg injected subcutaneously once a month for 12 months. Requires 2 injections to achieve the dose of 210 mg (give one after the other). Patients should also take supplemental calcium and vitamin D if dietary intake is not enough. No dosage adjustments for renal impairment; however, in patients receiving dialysis or who have a creatinine clearance less than 29 mL/minute, may increase the risk of hypocalcemia 8. Calcitonin-salmon (Miacalcin) a. Inhibition of bone resorption b.  Not first-line; reserved for short-term use for bone pain caused by vertebral compression fractures, no longer used frequently for osteoporosis therapy. Typically not recommended because of the weak effect on BMD. c. Efficacy: Nasal calcitonin reduces the incidence of new vertebral fractures by 36%. d. Adverse effects i. Nasal (10%–12%): Rhinitis, epistaxis, irritation, nasal sores, dryness, tenderness ii. Other (3%–5%): Backache, arthralgia, headache e. Drug interactions: None f. Dosage: 200 international units/day in one nostril, alternating nostrils daily g. FDA labeling changes regarding safety in 2014: Malignancies reported to be higher in those treated with calcitonin than in those treated with placebo. Benefits for patient should be discussed with patient and carefully considered. 9. Menopausal estrogen therapy or menopausal estrogen and progestogen therapy; (see Hormone Therapy and Menopause section earlier) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-569 Sexual & Reproductive Health 10. Lifestyle modifications a. Weight-bearing exercise (e.g., walking, tai chi, dancing, tennis); recommend 30–40 minutes per session most days of the week. b. Smoking cessation: Smokers tend to have lower BMD scores than nonsmokers and may reach menopause earlier. c. Limiting alcohol intake: Affects fall risk; 2 or more units of alcohol per day associated with 20% of falls at home; no more than 2 units/day or 7 units/week is recommended. d. Fall prevention Table 10. Postmenopausal Osteoporosis Treatment High Risk/No Prior Fractures First Line Alternative First Line Alendronate, Ibandronate, risedronate, raloxifene, zoledronate denosumab Increasing or Stable BMD and No Fractures Drug holiday (after 5 yr of PO or 3 yr of IV therapy) Resume therapy with a fracture, BMD declines, BTM rises to pretreatment value Very High Risk/Prior Fractures First Line Denosumab – continue until no longer high risk (up to 10 years); transition to another antiresorptive agent Progression of Bone Loss or Recurrent Fractures Assess adherence Change to injectable antiresorptive (if on PO therapy) If on injectable or at very high risk, change to abaloparatide, romosozumab, or teriparatide Alternative First Line Alendronate, risedronate Romosozumab × 1 yr – sequential therapy with PO or injectable antiresorptive agent Abaloparatide or teriparatide × 2 yr – sequential therapy with PO or injectable antiresorptive agent Zoledronate × 6 yr (if stable) – if progressive bone loss or recurrent fractures, change to abaloparatide, teriparatide, or romosozumab BMD = bone mineral density; BTM = bone turnover marker; IV = intravenous; PO = oral. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-570 Sexual & Reproductive Health Patient Case Questions 3 and 4 pertain to the following case: R.K. is a 71-year-old woman (height 63 inches, weight 64 kg) with a history of rheumatoid arthritis who smokes ½ pack/day. She is lactose intolerant and has minimal intake of dairy products. She takes calcium 1200 mg orally per day in divided doses and vitamin D 600 international units/day orally. Her calculated creatinine clearance (CrCl) is 60–70 mL/minute. Her BMD T-score is -2.6 at the hip and -2.1 at the spine. Her FRAX score indicates she has a 10-year probability of a major osteoporotic fracture of 22% and a 10-year probability of a hip fracture of 11%. 3. Which statement best describes the correct diagnosis for R.K.? A. She has normal BMD of the spine. B. She has low bone mass (osteopenia) of the hip. C. She has osteoporosis of the hip. D. She has severe osteoporosis of the spine. 4. Which is the best therapy for R.K.? A. No further treatment is needed; continue calcium 1200 mg/vitamin D 600 international units/day orally. B. Give abaloparatide 80 mcg subcutaneously daily, and continue calcium 1200 mg/vitamin D 600 international units/day orally. C. Give romosozumab 210 mg subcutaneously every month, continue calcium 1200 mg/day orally, and increase vitamin D to 800 international units/day orally. D. Give risedronate 35 mg orally every week; continue calcium 1200 mg orally per day, and increase vitamin D to 800 international units/day orally. III. DRUGS IN PREGNANCY A. Definitions and Overview 1. Teratogen: Drug or environmental agent with the potential to cause abnormal fetal growth and development 2. Teratogenicity: Capability of producing congenital abnormalities, major or minor malformations B. Causes of Defects 1. Genetic predisposition 25% 2. Drug 2%–3% 3. Unknown 72%–73% C. Factors That Influence Risk of Medication Use in Pregnancy 1. Genotypes of mother and fetus 2. Embryonic stage at exposure 3. Medication dose and duration 4. Simultaneous exposure to other drugs that may increase or decrease medication concentrations ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-571 Sexual & Reproductive Health 5. 6. Timing of exposure a. 1 month before conception: Folic acid 0.4 mg or more taken daily to prevent neural tube defects b. Around time of conception and implantation c. First 12–15 days after conception: If one cell is damaged, another can assume its function. d. First 3 months: Physical malformations e. Throughout pregnancy: Functional and behavioral defects because brain development occurs throughout pregnancy. Factors for placental transport a. Molecular weight of drug less than 400–600 Da crosses placenta; most drugs weigh 250–400 Da. b. Degree of protein binding; lower in fetus, so more free-drug concentration. c. Maternal and fetal blood flow usually equivalent; simple diffusion allows fetal drug concentration to be 50%–100% of maternal. d. Metabolic activity of the placenta; excretion of medications by the fetus occurs in liver and placenta. D. Risk Factor Categories 1. In 1979, the FDA introduced risk categories for drugs used during pregnancy. 2. The previous FDA pregnancy risk categories appear in Box 1. Box 1. Previous FDA Pregnancy Risk Categories A: Controlled studies of women fail to show risk. B: Animal studies indicate no risk, or animal studies show a risk that has not been shown in human studies. C: No available studies of women or animals, or animal studies have shown a risk. D: Positive evidence of fetal risk. X: Definite fetal risk in animals or women. 3. The FDA decided current pregnancy risk categories were inadequate; therefore, in 2008 the FDA recommended a new labeling system that became effective June 30, 2015 that includes the following: a. Pregnancy (includes labor and delivery) i. Fetal risk summary ii. Clinical considerations iii. Data section iv. Information for exposure registries b. Lactation c. Females and males of reproductive potential E. Factors to Consider When Initiating Medications in Pregnant Women (Boxes 2, 3, 4, and 5) 1. Risk-benefit ratio 2. Is drug necessary? 3. Most effective agent with least risk 4. Lowest effective dosage for shortest possible duration 5. Health of mother without drug ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-572 Sexual & Reproductive Health Box 2. Selected Known Teratogens Alcohol Androgens Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Anticonvulsants Antineoplastics Cocaine Diethylstilbestrol Fluconazole (high doses) Iodides Isotretinoin Lead Lithium Mercury Methimazole Methotrexate Paroxetine Penicillamine Statins Tetracyclines Thalidomide Vitamin A (higher than recommended daily doses) Warfarin Box 3. Examples of Drugs Used in Pregnancy (if benefit outweighs risk) Acetaminophen Cephalosporins Cetirizine Erythromycin Penicillin Pyridoxine/doxylamine Box 4. Some Drugs with Known Pregnancy Risks: Should Be Used with Caution Aminoglycosides Antithyroid drugs Aspirina Barbiturates Benzodiazepines Caffeine Chloramphenicol Diuretics Isoniazid Narcotic analgesics (chronic) Nicotine NSAIDs Oral hypoglycemics β-Blockers NSAIDs = nonsteroidal anti-inflammatory drugs a Daily low-dose aspirin (81 mg/day) is recommended in women at high risk of pre-eclampsia. This dose is considered safe and associated with a low likelihood of serious maternal and/or fetal complications. Box 5. Types of Adverse Effects After Fetal Drug Exposure Cancer Developmental delay or deficiency Fetal death Growth retardation Hematologic abnormalities Low birth weight for gestational age Metabolic abnormalities Renal dysfunction Seizures Sexual or reproductive dysfunction Teratogenic abnormalities Thyroid dysfunction Withdrawal ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-573 Sexual & Reproductive Health F. Resources for Medication Use During Pregnancy 1. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 11th Edition.Wolters Kluwer, 2017. a. Available as a textbook or online by subscription to Facts & Comparisons eAnswers online and Lexi-Comp. b. Provides information about medication use during pregnancy and lactation. 2. TERIS (Teratogen Information System, http://depts.washington.edu/terisdb/) and Shepard’s Database a. Available on its own by subscription or by a subscription to Micromedex Solutions. b.  Provides access to the Clinical Teratology Web (http://depts.washington.edu/terisdb/terisweb/ index.html) and has a list of several textbook references and websites not all listed here. 3. Diseases, Complications, and Drug Therapy in Obstetrics: A Guide for Clinicians. American Society of Health-System Pharmacists, 2009. a. Available as a textbook. b. Provides information on chronic disease management in pregnancy. 4. Organization of Teratology Information Specialists (OTIS): MotherToBaby (http://mothertobaby.org/) a. Available online by subscription. b. Has some resources available to public and providers such as information sheets. c. Free hotline for questions (866-626-6847) or e-mail an expert. 5. Micromedex Solutions: REPROTEXT and REPROTOX a. Available by purchase. b. Provides information about pregnancy, teratogenicity, and lactation and medication use. IV. DRUGS IN LACTATION A. Drugs That Decrease Milk Supply (Box 6) Box 6. Selected Drugs That Decrease Milk Supply Androgens Bromocriptine Ergot alkaloids Estrogen Levodopa Monoamine oxidase inhibitors (MAOIs) Nicotine Pyridoxine Sympathomimetics B. Drugs That Increase Milk Production (Galactagogues) (Box 7) Box 7. Selected Drugs That Increase Milk Production (Galactagogues) (may or may not be safe in breastfeeding) Amoxapine Antipsychotics Cimetidine C. Methyldopa Metoclopramide Reserpine Ways to Minimize Effects of Drugs During Breastfeeding 1. Choose drugs with short half-lives. 2. Administer drug immediately after a feeding or before a long sleep period. 3. Consider whether the drug is given to neonates. 4. Consider age and health status of the infant (e.g., concomitant medical conditions, preterm birth). 5. Short-term drug: Mother can pump and discard milk (“pump and dump”). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-574 Sexual & Reproductive Health D. Safe and Unsafe Drugs in Breastfeeding (Boxes 8 and 9) Box 8. Some Drugs Contraindicated in Breastfeeding According to the American Academy of Pediatrics Amphetamines Antineoplastics Benzodiazepines Bromocriptine Cocaine Drugs of abuse Ergotamine Kava Lithium Nicotine Pain medications (common ones include oxycodone, pentazocine, and meperidine) Yohimbe Herbs that lack safety data (chamomile, black cohosh, blue cohosh, chaste tree, echinacea, ginseng, ginkgo, St. John’s wort, valerian) Box 9. Relatively Safe Agents During Lactation Analgesics (ibuprofen, acetaminophen) Antibiotics (penicillins, cephalosporins, erythromycins) Caffeine (in moderation [1 or 2 cups/day]) Insulin E. Specific Resources for Drug Information Regarding Lactation 1. LactMed (http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm) a. Available through the U.S. National Library of Medicine. b. Available without purchase or subscription, although specific database is being phased out with information incorporated in other databases. c. Provides information about safety of medication use during lactation and provides alternative recommendations. 2. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 11th Edition. Wolters Kluwer, 2017. a. Available as a textbook or by subscription to Facts & Comparisons eAnswers online. b. Provides information about medication use during pregnancy and lactation. 3. Hale T. Medications and Mothers’ Milk a. Available by purchase; online site: www.halesmeds.com b. Provides information on medication use in lactation with a scoring system of safety. i. L1: Safest. Drug has been taken by many breastfeeding mothers with no observed increase in adverse effects in the infant ii. L2: Safer. Drug has been studied in a limited number of breastfeeding women with no increase in adverse effects in the infant iii. L3: Moderately safe. No controlled studies in breastfeeding women; however, adverse effects in the infant are possible iv. L4: Possibly hazardous. Positive evidence of risk to a breastfed infant or to breast milk production v. L5: Contraindicated. Studies of breastfeeding mothers have shown that there is risk to the infant, or there is a high risk of causing significant harm to the infant. 4. Micromedex solutions: REPROTEXT and REPROTOX a. Available by purchase. b. Provides information about pregnancy, teratogenicity, and lactation and medication use. 5. Organization of Teratology Information Specialists OTIS: MotherToBaby (http://mothertobaby.org/) a. Available online by subscription. b. Has some resources available to public and providers such as information sheets. c. Free hotline for questions (866-626-6847) or e-mail an expert. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-575 Sexual & Reproductive Health V. COMMON CONDITIONS DURING PREGNANCY A. Morning Sickness 1. Nausea and vomiting associated with pregnancy 2. Usually during first trimester, but can last throughout pregnancy. 3. Usually occurs upon rising and diminishes as day progresses 4. Cause: Unknown, although various theories have been proposed 5. Hyperemesis gravidarum: Severe nausea and vomiting leading to dehydration and malnutrition. 6. Nonmedical treatment: First line a. Eat saltine crackers. b. Keep stomach from becoming completely empty. c. Eat small, dry meals. d. Avoid spicy and odorous foods. 7. Symptomatic treatment a. Doxylamine and pyridoxine (Diclegis: doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg; dosage 2 tablets orally at bedtime daily. Maximum dosage: One tablet in the morning, one mid-afternoon, and two at bedtime. Bonjesta: doxylamine succinate extended release 20 mg and pyridoxine hydrochloride 20 mg; maximum dosage: 1 tablet in the morning, 1 tablet at bedtime) – considered first-line treatment after nonpharmacologic treatment. i. Diclegis and Bonjesta are the only FDA-approved medications for nausea and vomiting in pregnancy. Diclegis is a delayed-release formulation and Bonjesta is an extended-release formulation. Because of the cost or insurance coverage, physicians and patients have attempted off-label use of over-the-counter 12.5 mg doxylamine plus 10–25 mg pyridoxine; however, the efficacy of treatment appears diminished. b. Pyridoxine: Considered first-line treatment after nonpharmacologic treatment (with or without doxylamine). c. Dimenhydrinate d. Diphenhydramine e. Ondansetron: Only if nausea and vomiting not controlled with first-line agents; possibility of a slight increase in cardiac birth defects, mainly septal defects; best to avoid if possible, especially during first 10 weeks of gestation (Obstet Gynecol 2018;131:e15-e30). f. Metoclopramide – Only if nausea and vomiting not controlled with first-line agents. g. Phenothiazines – Only if nausea and vomiting not controlled with first-line agents. B. Heartburn 1. Occurs in latter half of pregnancy. 2. Cause: Enlarged uterus puts pressure on stomach, and esophageal sphincter relaxes. 3. Nonmedical treatment a. Smaller, more frequent meals b. Avoid food and liquids 3 hours before bed. c. Elevate head of bed with blocks. 4. Symptomatic relief a. Antacids i. Magnesium hydroxide ii. Aluminum hydroxide (overuse may lead to neurotoxicity) iii. Calcium carbonate b. Sucralfate: Not absorbed in GI tract. c. Second line: Famotidine, proton pump inhibitors ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-576 Sexual & Reproductive Health C. Constipation 1. Cause: Decreased peristalsis 2. Nonmedical treatment a. Increase high-fiber foods. b. Increase fluid intake to eight 8-oz glasses of water a day. c. Increase exercise. 3. Symptomatic relief a. Stool softeners (check that prenatal vitamin does not already contain docusate) b. Bulk laxatives: Not absorbed. c. Stimulants: Not recommended as first-line therapy. d. Avoid mineral oil: Impairs vitamin K absorption and could cause hypoprothrombinemia. D. Hemorrhoids 1. Caused by constipation and increased venous pressure below uterus 2. Correct constipation with stool softeners, appropriate hydration, and dietary fiber. 3. Sitz baths 4. Avoid topical anesthetics and steroids, not well studied. May be used short-term under a physician’s direction (Can Fam Physician 2008;54:189-90). E. Headache 1. Cause: Hormone fluctuations 2. Therapy a. Rest, ice packs b. Acetaminophen 3. Drugs to avoid a. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) b. Triptans, ergotamine F. Coagulation Disorders 1. Anticoagulation necessary a. History of VTE b. Prosthetic heart valve c. Deficiencies of clotting factors d. Antiphospholipid antibodies 2. Therapy a. Avoid warfarin (known teratogenicity) and direct oral anticoagulants (lack of data). b. Heparin or low-molecular-weight heparin (monitor for osteoporosis if heparin is used long term) c. Low-molecular-weight heparin preferred to heparin (Obstet Gynecol 2018;132:e18-34; Chest 2012; 141:e691S-736S). d. Dosing i. Prophylactic (a)  Enoxaparin 40 mg subcutaneously daily (b) Dalteparin 5000 units subcutaneously daily (c) Tinzaparin 4500 units subcutaneously daily (d) Heparin 5000–7500 units subcutaneously every 12 hours for first trimester, 7500–10,000 units subcutaneously every 12 hours for second trimester, and 10,000 units subcutaneously every 12 hours for third trimester unless activated partial thromboplastin time (aPTT) is elevated ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-577