Home

helps physicians and healthcare professionals

Erectile Dysfunction

helps physicians and healthcare professionals

Doctor123.org

helps physicians and healthcare professionals

Butorphanol


General


Pronunciation

(byoo TOR fa nole)


Indications


Use: Labeled Indications

Parenteral: Management of pain when the use of an opioid analgesic is appropriate; preoperative or preanesthetic medication; supplement to balanced anesthesia; management of pain during labor.

Nasal spray: Management of pain when the use of an opioid analgesic is appropriate.


Contraindications


Hypersensitivity to butorphanol or any component of the formulation


Dosing and Administration


Dosing: Adult

Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention. Butorphanol has an analgesic ceiling.

Pain:

IM: Initial: 2 mg, may repeat every 3-4 hours as needed; usual range: 1-4 mg every 3-4 hours as needed

IV: Initial: 1 mg, may repeat every 3-4 hours as needed; usual range: 0.5-2 mg every 3-4 hours as needed

Intranasal (spray): Initial: 1 spray (~1 mg per spray) in 1 nostril; if adequate pain relief is not achieved within 60-90 minutes, an additional 1 spray in 1 nostril may be given; may repeat initial dose sequence in 3-4 hours after the last dose as needed

Alternatively, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent (in the event drowsiness or dizziness occurs); additional 2 mg doses should not be given for 3-4 hours

Preoperative medication: IM: 2 mg 60-90 minutes before surgery

Supplement to balanced anesthesia:IV: 2 mg shortly before induction and/or an incremental dose of 0.5-1 mg (up to 0.06 mg/kg), depending on previously administered sedative, analgesic, and hypnotic medications

Pain during labor (fetus >37 weeks gestation and no signs of fetal distress):

IM, IV: 1-2 mg; may repeat in 4 hours

Note: Alternative analgesia should be used for pain associated with delivery or if delivery is anticipated within 4 hours


Dosing: Geriatric

IM, IV: Initial dosage should generally be 1/2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes if needed. In Canadian labeling, repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart.


Dosing: Renal Impairment

IM, IV: Initial dosage should generally be 1/2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes if needed. Repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart.

Canadian labeling: CrCl <30 mL/minute: Increase initial dosing interval to 6-8 hours.


Dosing: Hepatic Impairment

IM, IV: Initial dosage should generally be 1/2 of the recommended dose; repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart

Nasal spray: Initial dose should not exceed 1 mg; a second dose may be given after 90-120 minutes if needed. Repeated dosing must be based on initial response rather than fixed intervals, but generally should be at least 6 hours apart.

Canadian labeling: Increase interval of repeat dosing to 6-12 hours.


Administration

Intranasal: Prime pump prior to initial use and if it has not been used for ≥48 hours. Aim spray away from self and others when priming.


Storage

Injection: Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); protect from light.

Nasal spray: Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as tartrate:

Generic: 1 mg/mL (1 mL); 2 mg/mL (1 mL, 2 mL, 10 mL)

Solution, Injection, as tartrate [preservative free]:

Generic: 1 mg/mL (1 mL); 2 mg/mL (1 mL)

Solution, Nasal, as tartrate:

Generic: 10 mg/mL (2.5 mL)


Compatibility

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, midazolam.

Compatibility in syringe: Incompatible with dimenhydrinate, pentobarbital.


Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Analgesics (Opioid): Mixed Agonist / Antagonist Opioids may diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Exceptions: Buprenorphine; Butorphanol; Nalbuphine; Pentazocine. Avoid combination

Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: Mixed Agonist / Antagonist Opioids may diminish the therapeutic effect of Buprenorphine. This combination may also induce opioid withdrawal. Avoid combination

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification


Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure; signs or symptoms of hypogonadism or hypoadrenalism (Brennan, 2013)

Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]).


Adverse Reactions


>10%:

Central nervous system: Drowsiness (43%), dizziness (19%), insomnia (nasal spray 11%)

Gastrointestinal: Nausea and vomiting (13%)

Respiratory: Nasal congestion (nasal spray 13%)

1% to 10%:

Cardiovascular: Palpitations, vasodilatation

Central nervous system: Anxiety, burning sensation, confusion, euphoria, floating feeling, headache, lethargy, nervousness, paresthesia

Dermatologic: Cold and clammy skin, diaphoresis, pruritus

Gastrointestinal: Anorexia, constipation, stomach pain, unpleasant taste, xerostomia

Neuromuscular & skeletal: Tremor, weakness

Ophthalmic: Blurred vision

Otic: Otalgia, tinnitus

Respiratory: Bronchitis, cough, dyspnea, epistaxis, nasal discomfort, pharyngitis, rhinitis, sinus congestion, sinusitis, upper respiratory tract infection

<1% (Limited to important or life-threatening): Apnea, chest pain, convulsions, delusions, depression, drug dependence (prolonged use), dysphoria, edema, hallucinations, hives, hostility, hypertension, hypogonadism (Brennan, 2013; Debono, 2011), hypotension, respiratory depression, seizure, shallow respiration, skin rash, speech disturbance (transient), syncope, tachycardia, withdrawal syndrome


Warnings/Precautions


Special Populations: Renal Function Impairment

For those with creatinine clearance less than 30 mL/minute, the total body clearance is approximately one-half.


Special Populations: Hepatic Function Impairment

The total body clearance is approximately one-half.


Special Populations: Elderly

Absolute bioavailability of nasal spray is less in elderly women (48%) than in elderly men (75%).


Warnings/Precautions

Concerns related to adverse effects:

- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

- Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).

Disease-related concerns:

- Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

- Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

- Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.

- CNS depression/coma: Use with caution in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention.

- Drug abuse: Use opioids for chronic pain with caution in patients at increased risk for misuse; factors associated with increased risk include previous substance use disorder, younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages ( ≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).

- Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

- Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage adjustments are recommended in hepatic impairment.

- Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).

- Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

- Obesity: Use with caution in patients who are morbidly obese.

- Renal impairment: Use with caution in patients with renal impairment. Dosage adjustments are recommended in renal impairment.

- Respiratory disease: Use with caution in patients with preexisting respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.

- Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).

- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

- Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol. In the setting of chronic pain, avoid prescribing opioids and benzodiazepines concurrently whenever possible; epidemiologic studies suggest there is an increased risk for potentially fatal overdose with concurrent use (Dowell [CDC 2016]).

- Sumatriptan nasal spray: Concurrent use of sumatriptan nasal spray and butorphanol nasal spray may increase risk of transient high blood pressure.

Special populations:

- Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

- Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]).

- Neonates: Neonatal withdrawal syndrome: After chronic maternal exposure to opioids, neonatal withdrawal syndrome may occur in the newborn; monitor neonate closely. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. Opioid withdrawal syndrome in the neonate, unlike in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts.

Other warnings/precaution:

- Abuse/misuse/diversion: Health care provider should be alert to problems of abuse, misuse, and diversion.

- Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg. NSAIDs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).

- Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patients needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

- Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Butorphanol crosses the placenta. Butorphanol injection is approved for the management of pain during labor; apnea or respiratory distress in the newborn may occur. When used for pain relief during labor, opioids may temporarily affect the heart rate of the fetus (ACOG, 2002). The manufacturer recommends that caution be used if abnormal fetal heart rate patterns are present.

If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur; monitoring of the neonate is recommended. The minimum effective dose should be used if opioids are needed (Chou, 2009). Neonatal abstinence syndrome following opioid exposure may present with autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high pitched crying, increased muscle tone, irritability, seizure, tremor) symptoms (Dow, 2012; Hudak, 2012).


Actions


Pharmacology

Agonist of kappa opiate receptors and partial agonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces analgesia, respiratory depression, and sedation similar to opioids


Absorption

Rapid and well absorbed


Distribution

Vd: 305 to 901 L


Metabolism

Hepatic to major metabolite, hydroxybutorphanol


Excretion

Primarily urine (70% to 80%; ~5% unchanged); feces (15%)


Onset of Action

IM, Nasal: ≤15 minutes; IV: Within a few minutes

Peak effect: IM, IV: 0.5 to 1 hour; Nasal: 1 to 2 hours


Duration of Action

IM, IV: 3 to 4 hours; Nasal: 4 to 5 hours


Half-Life Elimination

IV, nasal: ~2-9 hours; Hydroxybutorphanol: ~18 hours

Elderly: IV, nasal: ~3 to 9 hours

Renal impairment (CrCl <30 mL/minute): 10.5 hours

Hepatic impairment: 16.8 hours


Protein Binding

~80%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, constipation, fatigue, rhinitis, or insomnia. Have patient report immediately to prescriber severe dizziness, passing out, difficulty breathing, slow breathing, shallow breathing, confusion, severe loss of strength and energy, abnormal heartbeat, tinnitus, urinary retention, severe headache, hallucinations, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss) sexual dysfunction (males), decreased libido, amenorrhea, infertility, or vision changes (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Copyright © 2016 - 2017
Doctor123.org | Disclaimer