Synarel
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nabilone
CesametApo-Nadolol, Corgard, Novo-NadololSynarelNubain
Pharmacologic class: Synthetic cannabinoid
Therapeutic class: Antiemetic
Controlled substance schedule II
Pregnancy risk category C
Pharmacologic class: Nonsteroidal anti-inflammatory drug (NSAID)
Therapeutic class: Antiarthritic
Pregnancy risk category C (first and second trimesters), D (third trimester)
Pregnancy risk category C (first and second trimesters), D (third trimester)
Pharmacologic class: Beta-adrenergic blocker (nonselective)
Therapeutic class: Antianginal, antihypertensive
Pregnancy risk category C
Pharmacologic class: Gonadotropin-releasing hormone (GnRH)
Therapeutic class: Hormone
Pregnancy risk category X
Pharmacologic class: Opioid agonist-antagonist
Therapeutic class: Analgesic, adjunct to anesthesia
Pregnancy risk category C
FDA Box Warning
Drug may increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. Risk may increase with duration of use. Patients with cardiovascular disease or risk factors for it may be at greater risk.
Drug increases risk of serious GI adverse events, including bleeding, ulcers, and stomach or intestinal perforation. These events can occur at any time during use and without warning. Elderly patients are at greater risk.
Drug is contraindicated for treatment of perioperative pain in setting of coronary artery bypass graft surgery.
Action
Unclear. Drug has complex effects on CNS, including relaxation, drowsiness, and euphoria; antiemetic effect may result from interaction with cannabinoid receptor system in neural tissues.
Availability
Capsules: 1 mg
⊘Indications and dosages
➣ Nausea and vomiting associated with cancer chemotherapy in patients who respond inadequately to conventional antiemetics
Adults: 1 to 2 mg P.O. twice daily; give initial dose 1 to 3 hours before chemotherapy. Maximum daily dose, 6 mg given in divided doses three times daily.
Contraindications
• Hypersensitivity to drug or other cannabinoids
Precautions
Use cautiously in:
• hepatic or renal impairment, hypertension, cardiac disease, QT interval prolongation, psychiatric disorders (current or previous)
• history of substance abuse
• concurrent use of sedatives, hypnotics, other psychoactive drugs, or CNS depressants
• concurrent alcohol use
• pregnant or breastfeeding patients
• elderly patients
• children (safety and efficacy not established).
Administration
• On day of chemotherapy, give 1 to 3 hours before chemotherapeutic drug is administered.
• To minimize adverse reactions, give recommended lower starting dosage and increase dosage as necessary.
• Know that drug may be given two or three times daily during entire course of each chemotherapy cycle and, if needed, for 48 hours after last dose of each chemotherapy cycle.

Adverse reactions
CNS: drowsiness, euphoria, dysphoria, inebriated feeling, mood swings, irritability, fatigue, malaise, ataxia, headache, poor concentration, disorientation, anxiety, depersonalization, depersonalization syndrome, speech disorder or disturbance, insomnia, abnormal dreams, vertigo, light-headedness, dizziness, orthostatic dizziness, twitching, depression, confusion, asthenia, sedation, hallucinations, paresthesia, memory disturbance, perception disturbance, seizures, dystonia, numbness, akathisia, tremor, incoordination, toxic psychosis, paranoia, apathy, thought disorder, panic disorder, withdrawal, nervousness, phobic neurosis, emotional disorder, hyperactivity, hypotonia, sinus headache
CV: orthostatic hypotension
EENT: visual disturbances, pharyngitis, nasal congestion, dry throat, dry nose, nosebleed, voice change, thick tongue sensation
GI: nausea, dry mouth
GU: increased or decreased urination, urinary retention, urinary frequency
Metabolic: thirst
Musculoskeletal: muscle pain, back pain, neck pain, joint pain
Respiratory: dyspnea, wheezing, cough
Skin: excessive sweating, pruritus, rash, photosensitivity
Other: taste changes, increased appetite, fever, hot flashes, chills, unspecified pain, bacterial infection, chest pain, allergic reaction
Interactions
Drug-drug.Amitriptyline, amoxapine, desipramine, other tricyclics: additive tachycardia, hypertension, drowsiness
Amphetamines, cocaine, other sympathomimetics: additive hypertension, tachycardia, possible cardiotoxicity
Anticholinergics, antihistamines, tri-cyclic antidepressants: increased tachycardia and hypertension
Antihistamines, atropine, scopolamine, other anticholinergics: additive or superadditive tachycardia, drowsiness
Antihistamines, barbiturates, benzodiazepines, buspirone, lithium, muscle relaxants, opioids, other CNS depressants: additive drowsiness and CNS depression
Antipyrine, barbiturates: decreased clearance of these drugs
Disulfiram, fluoxetine: reversible hypomanic reaction
Opioids: cross-tolerance and mutual potentiation
Naltrexone: enhanced nabilone effects
Theophylline: increased theophylline metabolism
Drug-behaviors.Alcohol use: increased positive mood effects, increased CNS depression
Sun exposure: increased risk of skin reactions
Patient monitoring
• Ensure that patient remains under supervision of responsible adult, especially during initial use and dosage adjustments.
• Monitor vital signs for orthostatic hypotension and tachycardia.
Check for adverse CNS reactions. Report significant depression, paranoid reaction, or emotional lability. Be aware that adverse psychiatric reactions can last for 48 to 72 hours after treatment ends.
• Monitor for excessive use, abuse, or misuse of drug.
• Monitor patient's nutritional and hydration status.
Patient teaching
• Instruct patient to take drug on day of chemotherapy 1 to 3 hours before chemotherapeutic drug is scheduled.
• Teach patient about significant CNS side effects (especially mood changes) and cardiovascular side effects. Stress importance of taking drug only as prescribed and needed.
• Inform patient that drug may cause additive CNS depression if used with alcohol or other CNS depressants (such as sleeping pills, tranquilizers, or anxiolytics).
Advise patient, family member, or caregiver to immediately report depression, suicidal thoughts, paranoid reactions, and other serious CNS reactions.
• Caution patient to avoid driving and other hazardous activities until drug effects are known.
• Instruct breastfeeding patient not to use drug while breastfeeding.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs and behaviors mentioned above.
nabumetone
Gen-Nabumetone, Nabumetone, Novo-Nabumetone, Relifex (UK), Sandoz
Pharmacologic class: Nonsteroidal anti-inflammatory drug (NSAID)
Therapeutic class: Antiarthritic
Pregnancy risk category C (first and second trimesters), D (third trimester)
FDABOXED WARNING
Drug may increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. Risk may increase with duration of use. Patients with cardiovascular disease or risk factors for it may be at greater risk.
Drug increases risk of serious GI adverse events, including bleeding, ulcers, and stomach or intestinal perforation. These events can occur at any time during use and without warning. Elderly patients are at greater risk.
Drug is contraindicated for treatment of perioperative pain in setting of coronary artery bypass graft surgery.
Action
Unknown. Thought to stimulate anti-inflammatory response and block pain impulses by inhibiting cyclooxygenase, an enzyme needed for prostaglandin synthesis.
Availability
Tablets: 500 mg, 750 mg
Indications and dosages
➣ Rheumatoid arthritis; osteoarthritis
Adults: 1,000 mg/day P.O. as a single dose or in two divided doses; may increase up to 2,000 mg/day
Contraindications
• Hypersensitivity to drug
• Active GI bleeding or ulcer disease
• History of aspirin- or NSAID-induced asthma, urticaria, or other allergic-type reaction
• Concurrent use of other NSAIDs
• Pregnancy (third trimester)
Precautions
Use cautiously in:
• severe cardiovascular, renal, or hepatic disease
• history of ulcer disease
• pregnant (first or second trimester) or breastfeeding patients
• children (safety and efficacy not established).
Administration
• Give with food or milk to increase absorption.
• In chronic therapy, use lowest effective dosage.

Adverse reactions
CNS: dizziness, drowsiness, fatigue, headache, insomnia, malaise, nervousness
CV: vasculitis
EENT: abnormal vision, tinnitus
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, stomatitis, dry mouth, GI bleeding
Skin: pruritus, rash, angioedema
Other: edema, fluid retention, allergic reactions including anaphylaxis
Interactions
Drug-drug.Acetaminophen: increased risk of adverse renal reactions (with chronic nabumetone use)
Anticoagulants, cefamandole, cefoperazone, cefotetan, clopidogrel, eptifibatide, plicamycin, thrombolytics, ticlopidine, tirofiban, valproic acid: increased risk of bleeding
Antihypertensives, diuretics: decreased nabumetone efficacy
Antineoplastics: increased risk of adverse hematologic reactions
Aspirin, corticosteroids, other NSAIDs, potassium supplements: additive adverse GI effects
Cyclosporine: increased risk of renal toxicity
Insulins, oral hypoglycemics: increased hypoglycemic effect
Methotrexate: increased risk of methotrexate toxicity
Patient monitoring
Watch closely for signs and symptoms of angioedema, anaphylaxis, or other hypersensitivity reactions (including hives, swelling, shortness of breath, and abdominal pain).
• Monitor GI status. Report nutritional deficiencies.
• Assess vital signs.
• Monitor fluid intake and output.
Patient teaching
• Tell patient he may crush tablet if he can't swallow it whole.
• To minimize GI upset, advise patient to take drug with food; eat small, frequent servings of healthy food; and drink plenty of fluids.
• Advise patient to continue taking drug for entire duration prescribed.
Teach patient to recognize and immediately report signs and symptoms of hypersensitivity reaction and angioedema (hives, swelling, shortness of breath, abdominal pain).
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, strength, and alertness.
• Advise patient not to drink alcohol. Tell him to avoid aspirin, ibuprofen, and over-the-counter preparations (unless prescribed).
• Caution female patient not to take drug, especially during third trimester.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.
nadolol
Pharmacologic class: Beta-adrenergic blocker (nonselective)
Therapeutic class: Antianginal, antihypertensive
Pregnancy risk category C
FDABOXED WARNING
Catecholamine hypersensitivity may occur after drug withdrawal. Angina exacerbation and in some cases, myocardial infarction have followed abrupt withdrawal. When discontinuing long-term nadolol, reduce dosage gradually over 1 to 2 weeks and monitor patient carefully. If angina worsens markedly or acute coronary insufficiency develops, reinstate drug promptly and take other appropriate measures to manage angina. Caution patient not to interrupt or stop therapy without physician's advice. Because coronary artery disease is common and may be unrecognized, don't discontinue drug abruptly, even in patients treated only for hypertension.
Action
Blocks stimulation of beta1-and beta2-adrenergic receptor sites, decreasing cardiac output and thereby slowing heart rate and reducing blood pressure
Availability
Tablets: 20 mg, 40 mg, 80 mg, 120 mg, 160 mg
⊘Indications and dosages
➣ Angina pectoris
Adults: Initially, 40 mg P.O. daily; may increase by 40 to 80 mg q 3 to 7 days p.r.n., up to a maximum of 240 mg/day
➣ Hypertension
Adults: Initially, 40 mg P.O. daily; may increase by 40 to 80 mg q 7 days p.r.n., up to 320 mg/day
Dosage adjustment
• Renal impairment
Off-label uses
• Hyperthyroidism
• Migraine headache
• Parkinson's tremor
Contraindications
• Hypersensitivity to drug or other beta-adrenergic blockers
• Pulmonary edema or cardiogenic shock
• Sinus bradycardia or heart block
• Heart failure (unless secondary to tachyarrhythmia treatable with beta blockers)
• Bronchial asthma (including severe chronic obstructive pulmonary disease)
Precautions
Use cautiously in:
• renal or hepatic impairment, pulmonary disease, diabetes mellitus, thyrotoxicosis
• history of severe allergic reactions
• elderly patients
• pregnant or breastfeeding patients
• children (safety not established).
Administration
• Give with or without food.
• Be aware that drug may be given alone or with diuretic for hypertension.

Adverse reactions
CNS: dizziness, fatigue, paresthesia, behavior changes, sedation
CV: bradycardia, peripheral vascular insufficiency (Raynaud's phenomenon), heart failure
EENT: blurred vision, dry eyes, nasal congestion
GI: nausea, constipation, diarrhea, abdominal discomfort or bloating, indigestion, anorexia
Respiratory: bronchospasm
Skin: rash
Interactions
Drug-drug.Amphetamines, ephedrine, epinephrine, norepinephrine, phenylephrine, pseudoephedrine: severe vasoconstriction and bradycardia
Antihypertensives, nitrates: additive hypotension
Clonidine: increased hypotension and bradycardia
Digoxin: additive bradycardia
Diltiazem, general anesthestics, phenytoin (I.V.), verapamil: additive myocardial depression
Insulins, oral hypoglycemics: altered glycemic control
Nonsteroidal anti-inflammatory drugs: decreased antihypertensive action
Thyroid hormones: decreased nadolol efficacy
Drug-behaviors.Acute alcohol ingestion: additive hypotension
Cocaine use: severe vasoconstriction, bradycardia
Patient monitoring
• Monitor vital signs and peripheral circulation. Notify prescriber of heart rate below 55 beats/minute.
• Assess for signs and symptoms of heart failure or bronchospasm.
Patient teaching
• Advise patient to take drug with meals and a bedtime snack to minimize GI upset.
• Teach patient how to measure pulse and blood pressure; tell him when to notify prescriber.
• Instruct patient to avoid over-the-counter products containing stimulants, such as some cold and flu remedies and nasal decongestants.
• Tell diabetic patient and family that drug may mask hypoglycemia symptoms. Advise patient to monitor urine or blood glucose regularly.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and behaviors mentioned above.
nafarelin acetate
Pharmacologic class: Gonadotropin-releasing hormone (GnRH)
Therapeutic class: Hormone
Pregnancy risk category X
Action
Inhibits secretion of gonadotropin, a luteinizing hormone (LH)-releasing hormone. Initially increases pituitary production of LH and follicle-stimulating hormone (FSH), which ultimately leads to deactivation of testicular and ovarian functions.
Availability
Nasal spray: 2 mg/ml in 10-ml bottle (200 mcg/spray)
⊘Indications and dosages
➣ Endometriosis
Adults: One spray (200 mcg) intra-nasally in one nostril in morning and one spray in other nostril in evening (400 mcg/day). May increase to one spray in each nostril in morning and evening (800 mcg/day).
➣ Central precocious puberty
Children: Two sprays in each nostril in morning and evening (1,600 mcg/day). May increase up to 1,800 mcg/day (three sprays in alternating nostrils t.i.d.).
Contraindications
• Hypersensitivity to GnRH, its analogs, or sorbitol
• Undiagnosed abnormal vaginal bleeding
• Pregnancy or breastfeeding
Precautions
Use cautiously in:
• rhinitis, ovarian cysts, major risk factors for bone density loss (such as chronic alcoholism or chronic corticosteroid use).
Administration
• Make sure patient isn't pregnant before starting therapy.
• For endometriosis, start therapy on day 2 to day 4 of menstrual period.
• If patient needs topical decongestant, wait at least 2 hours after nafarelin dose before giving.
• Know that retreatment for endometriosis isn't recommended.

Adverse reactions
CNS: emotional lability, headache, depression, insomnia, seizures
CV: chest pain, thromboembolism
EENT: nasal irritation, rhinitis
GU: vaginal dryness, bleeding, or discharge; menses cessation; transient breast enlargement; decreased libido
Musculoskeletal: reduced bone density, myalgia
Respiratory: dyspnea
Skin: urticaria, rash, pruritus, acne, oily skin, hirsutism, transient pubic hair increase
Other: weight changes, hot flashes, edema, body odor, hypersensitivity reaction
Interactions
Drug-drug.Topical nasal decongestants: reduced nafarelin absorption
Patient monitoring
• Monitor patient for emotional lability or depression.
• Assess nasal mucosa for erosion.
• Monitor vital signs. Weigh patient regularly; report edema.
• Stay alert for adverse hormonal effects, including hot flashes, menses cessation followed by breakthrough bleeding, hirsutism, acne, decreased libido, and vaginal dryness.
Closely monitor patient for signs and symptoms of seizures and thromboembolism.
Patient teaching
• Instruct patient to complete entire course of therapy. Advise her to keep enough of drug on hand to prevent interruption.
• Inform patient that regular menstruation should cease after 4 to 6 weeks of therapy but that breakthrough bleeding may still occur.
• Tell patient ovulation may still occur. Instruct her to use barrier contraception during therapy and to report suspected pregnancy.
• Caution patient not to breastfeed.
• Teach patient about adverse hormonal effects. Identify which signs and symptoms to report.
• Inform patient that drug may cause emotional changes or depression. Advise her to report these to prescriber.
Instruct patient to immediately report signs and symptoms of seizures and thromboembolism.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.
nalbuphine hydrochloride
Pharmacologic class: Opioid agonist-antagonist
Therapeutic class: Analgesic, adjunct to anesthesia
Pregnancy risk category C
Action
Binds to opiate receptors in CNS, inhibiting ascending pain pathways. This inhibition alters perception of and response to painful stimuli.
Availability
Injection: 10 mg/ml, 20 mg/ml
⊘Indications and dosages
➣ Moderate to severe pain
Adults: 10 mg/70 kg I.V., I.M., or subcutaneously q 3 to 6 hours p.r.n., up to 160 mg/day. Maximum for single dose is 20 mg.
➣ Adjunct to balanced anesthesia
Adults: 0.3 mg to 3 mg/kg I.V. over 10 to 15 minutes, followed by maintenance dose of 0.25 mg to 0.50 mg/kg I.V. in single doses p.r.n.
Contraindications
• Hypersensitivity to drug
Precautions
Use cautiously in:
• increased intracranial pressure, head trauma, myocardial infarction, severe heart disease, respiratory depression, renal or hepatic disease, impaired ventilation, hypothyroidism, adrenal insufficiency, prostatic hypertrophy, emotional instability, alcoholism
• history of substance abuse or dependence
• pregnant or breastfeeding patients
• children.
Administration
Make sure emergency resuscitation equipment and naloxone (antidote) are available before starting therapy.
• For I.M. use, inject deep into large muscle mass; rotate injection sites.
• When giving I.V. for pain, infuse undiluted over 2 to 3 minutes into vein or I.V. line with compatible solution (such as dextrose 5% in water, normal saline solution, or lactated Ringer's solution).

Adverse reactions
CNS: dizziness, sedation, headache, vertigo
CV: hypertension, hypotension, tachycardia, bradycardia
EENT: miosis
GI: nausea, vomiting, dry mouth
Respiratory: dyspnea, respiratory depression
Skin: sweating, clammy skin
Other: hypersensitivity reactions including anaphylaxis
Interactions
Drug-drug.CNS depressants (including general anesthetics, MAO inhibitors, sedative-hypnotics, tranquilizers, tricyclic antidepressants): additive CNS effects
Drug-diagnostic tests.Amylase, lipase: increased levels
Drug-herbs.Chamomile, hops, kava, skullcap, valerian: increased CNS depression
Drug-behaviors.Alcohol use: additive CNS and respiratory depression
Patient monitoring
• Monitor vital signs. Watch for respiratory depression and heart rate changes.
• Evaluate patient for CNS changes. Institute safety measures as needed to prevent injury.
Watch for hypersensitivity reactions, including anaphylaxis.
Patient teaching
• Instruct patient to change position slowly and carefully to avoid dizziness from sudden blood pressure decrease.
• Tell patient to avoid CNS depressants (including alcohol, sedative-hypnotics, and some herbs) for at least 24 hours after taking nalbuphine.
• Advise patient to consult prescriber before taking herbs.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.
naproxen
Apo-Naproxen, EC-Naprosyn, Gen Naproxen, Naprosyn, Naprosyn-E, Naprosyn-EC (UK), Naprosyn SR, Novo-Naprox, Nu-Naprox, Nycopren (UK), PMS-Naproxen EC, Riva-Naproxen
nafarelin
(na-fare-e-lin) ,Synarel
(trade name)Classification
Therapeutic: hormonesPharmacologic: gonadotropin releasing hormones
Indications
Action
Therapeutic effects
Pharmacokinetics
Time/action profile (↓ ovarian steroid production)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
Intranasal | within 4 wk | 3–4 wk | 3–6 mo† |
Contraindications/Precautions
Adverse Reactions/Side Effects
Central nervous system
- stroke (life-threatening)
- emotional instability (most frequent)
- headaches (most frequent)
- depression
- insomnia
Ear, Eye, Nose, Throat
- nasal irritation (most frequent)
Cardiovascular
- Myocardial infarction (life-threatening)
- edema
Genitourinary
- vaginal dryness (most frequent)
Dermatologic
- acne (most frequent)
- hirsutism
- seborrhea
Endocrinologic
- cessation of menses (most frequent)
- impaired fertility (most frequent)
- ↓ breast size (most frequent)
Metabolic
- hyperglycemia
Musculoskeletal
- ↓ bone density
- myalgia
Miscellaneous
- ↓ libido (most frequent)
- hot flashes (most frequent)
- hypersensitivity reactions
- weight gain
Interactions
Drug-Drug interaction
Concurrent topical nasal decongestants may ↓ absorption of nafarelin (administer decongestant at least 2 hr after nafarelin).Route/Dosage
Availability
Nursing implications
Nursing assessment
- Endometriosis: Assess patient for endometriotic pain periodically during therapy.
- Central Precocious Puberty: Prior to therapy, a complete physical and endocrinologic examination including height, weight, hand and wrist x-ray, total sex steroid level (estradiol or testosterone), adrenal steroid level, beta human chorionic gonadotropin level, GnRH stimulation test, pelvic/adrenal/testicular ultrasound, and CT of the head must be performed. These parameters are monitored after 6–8 wk and every 3–6 mo during therapy.
- Assess patient for signs of precocious puberty (menses, breast development, testicular growth) periodically during therapy.
- Nafarelin is discontinued when the onset of normal puberty is desired. Monitor the onset of normal puberty and assess menstrual cycle, reproductive function, and final adult height.
Potential Nursing Diagnoses
Acute pain (Indications)Sexual dysfunction (Indications, Side Effects)
Implementation
- Endometriosis: Treatment should be started between days 2 and 4 of the menstrual cycle and continued for up to 6 mo.
Patient/Family Teaching
- Instruct patient on the correct technique for nasal spray: The head should be tilted back slightly; wait 30 sec between sprays.
- Advise patient to consult health care professional if rhinitis occurs during therapy. If a topical decongestant is needed, do not use decongestant until 2 hr after nafarelin dosing. If possible, avoid sneezing during and immediately after nafarelin dose.
- Endometriosis: Inform patient that 1 spray should be administered into 1 nostril in the morning and 1 spray into the other nostril in the evening for the 400 mcg/day dose. If dose is increased to 800 mcg/day, administer 1 spray to each nostril (2 sprays) morning and evening; 1 bottle should provide a 30-day supply at the 400 mcg/day dose.
- Advise patient to use a form of contraception other than oral contraceptives during therapy. Inform patient that amenorrhea is expected. Instruct patient to notify health care professional if regular menstruation persists or if successive doses are missed.
- Advise patient that medication may cause hot flashes. Notify health care professional if these become bothersome.
- Central Precocious Puberty: Instruct patient on correct timing and number of sprays. The 1600 mcg/day dose is achieved by 2 sprays to each nostril in the morning (4 sprays) and 2 sprays to each nostril in the evening (4 sprays), for a total of 8 sprays. The 1800 mcg/day dose is achieved by 3 sprays into alternating nostrils 3 times per day, for a total of 9 sprays. Inform patient and parents that if doses are not taken as directed pubertal process may be reactivated. One bottle should provide a 7-day supply at the 1600 mcg/day dose.
- Advise patient and parents that during 1st mo of therapy some signs of puberty (vaginal bleeding, breast enlargement) may occur. These should resolve after the 1st mo of therapy. If these signs persist after the 2nd mo of therapy, notify health care professional.
Evaluation/Desired Outcomes
- Reduction in lesions and associated pain in endometriosis.
- Resolution of the signs of precocious puberty.