Saturday Botanical: Andrographis paniculata

BOTANICAL NAME/FAMILY

• Andrographis paniculata (family Acanthaceae)

OTHER NAMES

• Andrographis, chirayata, chiretta, green chiretta, Indian echinacea, kalmegh, king of bitters

PLANT PARTS USED

·        Leaves, aerial parts

CHEMICAL COMPONENTS

• The main active constituent group is considered to be the bitter diterpenoid lactones known as andrographolides. This group consists of andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4).
• Other constituents include diterpenoid glucosides, diterpene dimers, flavonoids and xanthones.

MAIN ACTIONS                                

·        Immunomodulating via constituent andrographolide by decreasing IFN-gamma and IL-2.

Other actions include

·        Anti-cancer, antimicrobial, antimalarial, cardiovascular support(prevents atherosclerotic build up, prevention of myocardial reperfusion injury, and antihypertensive), hypoglycemic, hepatoprotective, digestive stimulant/choleretic, antipyretic, anti-inflammatory, antiplatelet and antithrombotic activity.

DOSAGE RANGE

·       Prevention dose

1200–3000 mg andrographis (standardised to contain no less than 11.2 mg andrographolides) or 4–6 mL of 1:2 liquid extract, daily in divided doses, taken for at least 3 months for preventive effects to become established.

·       Treatment dose for infection

1200–6000 mg/day or fluid extract (1:2): up to 12 mL/day or equivalent in solid dose form.

 ADVERSE REACTIONS

• Generally well tolerated, but high doses may cause vomiting, anorexia and gastrointestinal discomfort. One source states that urticaria is also possible

SIGNIFICANT INTERACTIONS

·       Anticoagulants

Increased risk of bruising and bleeding is theoretically possible, because andrographolide and other constituents in andrographis inhibit PAF-induced platelet aggregation. However andrographis used together with warfarin did not produce any significant effects on the pharmacokinetics of warfarin, and had even less effect on its pharmacodynamics in vivo. Caution should still be exercised until further research is available.

·       Antiplatelet drugs

Additive effects are possible, because the herb exhibits antiplatelet activity — observe the patient.

·       Barbiturates

Additive effects are possible, according to an animal study — observe the patient. Beneficial interaction is theoretically possible under professional supervision.

·       Hepatotoxic drugs (paracetamol, tricyclic antidepressants)

Hepatoprotection is possible, according to studies in various experimental models — interaction is beneficial.

·       Hypoglycaemic agents

Additive effects are theoretically possible — andrographis has hypoglycaemic activity comparable to that of metformin in vivo. Use together with caution; however, interaction may be beneficial.

·       Drugs metabolised chiefly via the cytochrome p450 system

It is currently unclear whether there is a significant interaction between andrographis and these medications, as in vivo evidence is suggestive of enzyme induction, but this observation has not yet been investigated in clinical studies. Recently andrographolide was shown to strongly induce the CYP 1A1 induction pathway; however, the clinical significance of this is unknown. Another in vitro study has demonstrated an inhibitive effect of andrographis extract and andrographolide on CYP3A and 2C9 pathways. It is recommended that patients be observed to ensure that drug effectiveness is not compromised.

·       Immunosuppressants

Reduced drug activity is theoretically possible, as immunostimulant activity has been demonstrated in vivo — use caution in the immunosuppressed.

CONTRAINDICATIONS AND PRECAUTIONS

• Suspend use of concentrated extracts 1 week before major surgery.

 PREGNANCY USE

Not recommended for use in pregnancy. There is conflicting evidence about the safety of andrographis in pregnancy.

Friday's Botanical: Aloe vera

BOTANICAL NAME/FAMILY

·        Aloe vera (L.)/Aloe barbadensis (Mill.) (family Aloeaceae)

OTHER NAMES

·        Aloes, Barbados aloe, Curacao aloe

PLANT PARTS USED

·        leaf

CHEMICAL COMPONENTS

·        Aloe vera extract, or diluted aloe gel, is made of mostly water (99%) and mono- and polysaccharides, the most important of which are the monosaccharide mannose-6-phosphate and the polysaccharide gluco-mannans, which are long-chain sugars containing glucose and mannose. Gluco-mannan has been named acemannan and is marketed as Carrisyn. A glycoprotein with anti-allergic properties has also been isolated, and has been named alprogen. Recently, C-glucosyl chromone, an anti-inflammatory compound, has also been identified.

·        Aloe gel also contains lignans, saponins, salicylic acid, sterols and triterpenoids, vitamins A, C, E, B₁₂, thiamine, niacin and folic acid, and the minerals sodium, calcium, potassium, manganese, magnesium, copper, chromium, zinc and iron

MAIN ACTIONS                       

·        The active ingredients, whether acting alone or in concert, include glycoproteins, anthraquinones, polysaccharides, and low-molecular-weight species such as beta-sitosterol. 

·        Assists in wound healing

Wound healing is associated with various mechanisms and constituents. Thromboxane inhibits wound healing and aloe has been shown to inhibit thromboxane in vitro. Enzymes in aloe have also been shown to break down damaged tissue, which can then be removed by phagocytosis. A glycoprotein fraction was found to increase proliferation of human keratinocytes and increase the expression of receptors for epidermal growth factor and fibronectin in vitro. The same research team then demonstrated that this glycoprotein enhanced wound healing by increasing cell proliferation in vivo. Beta-sitosterol appears to improve wound healing by stimulating angiogenesis and neovascularisation in vivo. Aloe polysaccharides have been shown to ameliorate UV-induced immunosuppression.

Other actions include

·        Anti-oxidant, immunostimulant, anti-inflammatory, laxative, anti-ulcer, hypoglycaemic, antimicrobial, antiviral.

DOSAGE RANGE

·        Aloe vera gel: fresh from a living plant or as stabilised juice 25 mL (4.5:1) up to four times daily.

·        Extracts standardised to acemannan: preparation containing up to 800 mg/day.

·        Topical application: gel, cream or ointment as needed.

·        1.5–4.5 mL daily of 1:10 tincture of resin (latex).

ADVERSE REACTIONS

·        Although adverse reactions are rare, hypersensitivities and contact dermatitis to aloe have been.  Hypersensitivity manifested by generalised nummular eczematous and papular dermatitis, and presumably by contact urticaria, developed in a 47-year-old man after 4 years of using oral and topical aloe. Patch tests for aloe were positive in this patient.

SIGNIFICANT INTERACTIONS

·        Hypoglycaemic agents

o       Oral A. vera may have hypoglycaemic activity, therefore additive effects are theoretically possible— observe patients taking this combination.

·        Laxatives

o       Additive effects are theoretically possible with oral aloe latex inducing griping pains. Use with caution.

·        Topical cortisone preparations

o       In addition to its own anti-inflammatory effects, animal studies have shown that A. vera increases the absorption of hydrocortisone by hydrating the stratum corneum, inhibits hydrocortisone’s suppressive effects on wound healing and increases wound tensile strength — possible beneficial interaction.

·        Vitamins C and E

o       Concurrent prescription of oral A. vera (both gel and latex) with vitamins C and E shows improved absorption and increased plasma life of vitamin concentration for both vitamins when taken together.

CONTRAINDICATIONS AND PRECAUTIONS

o       Strong laxatives such as aloe latex are contraindicated in children. Avoid in patients with known hypersensitivity to aloe or with nausea, vomiting or signs and symptoms of gastrointestinal obstruction. Avoid excessive use and long-term use (more than 2 weeks), as potassium losses may occur, which may alter cardiac electrophysiology.

o       Use with caution in people with thyrotoxicosis.

PREGNANCY USE

o       Strong laxatives such as aloe latex are traditionally contraindicated in pregnancy. Scientific evidence is unavailable to conclusively support the safe use of orally administered aloe.

Fluororuracil

Today's med: Fluorouracil (flure oh YOOR a sil)  

(brand names: Adrucil, Carac, Efudex, Fluoroplex)  

Index terms: 5-FU, 5-Fluorouracil, 5-Fluracil, Fluoro Uracil, Florouracil, FU)

Drug Class: Nucleoside Metabolic Inhibitor (Chemotherapeuitic agent) 

Antimetabolite (Pyrimidine Analog)

Other Drugs in this class: Capecitabine, Gemcitabine, Cytarabine,Azacitidine, 

Fludarabine, Decitabine, Clofarabine, Pentostatin, Nelarabine,Gemcitabine hydrochloride, Fludarabine Phosphate

Indications: 

Use: Labeled Indications

Treatment of breast cancer, colon cancer, rectal cancer, pancreatic cancer, and stomach (gastric) cancer

Use: Unlabeled

Treatment of anal cancer, bladder cancer, cervical cancer, esophageal cancer, head and neck cancer, hepatobiliary cancers, neuroendocrine tumors, penile cancer (metastatic), thymic cancers, and unknown primary cancer

Contraindications: Hypersensitivity to fluorouracil or any component of the formulation; poor nutritional states; depressed bone marrow function; potentially serious infections.

Adverse Effects:  Cardiovascular: Angina, arrhythmia, heart failure, MI, myocardial ischemia, vasospasm, ventricular ectopy; Central nervous system: Acute cerebellar syndrome, confusion, disorientation, euphoria, headache, nystagmus, stroke; Dermatologic: Alopecia, dermatitis, dry skin, fissuring, nail changes (nail loss), palmar-plantar erythrodysesthesia syndrome, pruritic maculopapular rash, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, vein pigmentation

Gastrointestinal: Anorexia, bleeding, diarrhea, esophagopharyngitis, mesenteric ischemia (acute), nausea,

sloughing, stomatitis, ulceration, vomiting; Hematologic: Agranulocytosis, anemia, leukopenia (nadir: days;

9-14; recovery by day 30), pancytopenia, thrombocytopenia; Local: Thrombophlebitis; Ocular: Lacrimation,

lacrimal duct stenosis, photophobia, visual changes;  Respiratory: Epistaxis; Miscellaneous: Anaphylaxis,

generalized allergic reactions

Standard Dosing: I.V.: Administration rate varies by protocol; refer to specific reference for protocol. May be administered by I.V. push, I.V. bolus, or as a continuous infusion. Avoid extravasation (may be an irritant).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH, 2012).  

**Increase dietary intake of thiamine.

Breast cancer (unlabeled dosing): I.V.:

CEF regimen: 500 mg/m² on days 1 and 8 every 28 days (in combination with cyclophosphamide and epirubicin) for 6 cycles (Levine, 1998)

CMF regimen: 600 mg/m² on days 1 and 8 every 28 days (in combination with cyclophosphamide and methotrexate) for 6 cycles (Goldhirsch, 1998; Levine, 1998)

FAC regimen: 500 mg/m² on days 1 and 8 every 21-28 days (in combination with cyclophosphamide and doxorubicin) for 6 cycles (Assikis, 2003)

Colorectal cancer (unlabeled dosing): I.V.:

FLOX regimen: 500 mg/m² bolus on days 1, 8, 15, 22, 29, and 36 (1 hour after leucovorin) every 8 weeks (in combination with leucovorin and oxaliplatin) for 3 cycles (Kuebler, 2007)

FOLFOX6 and mFOLFOX6 regimen: 400 mg/m² bolus on day 1, followed by 1200 mg/m²/day continuous infusion for 2 days (over 46 hours) every 2 weeks (in combination with leucovorin and oxaliplatin) until disease progression or unacceptable toxicity (Cheeseman, 2002)

FOLFIRI regimens: 400 mg/m² bolus on day 1, followed by 1200 mg/m²/day continuous infusion for 2 days (over 46 hours) every 2 weeks (in combination with leucovorin and irinotecan) until disease progression or unacceptable toxicity; after 2 cycles, may increase continuous infusion fluorouracil dose to 1500 mg/m²/day (over 46 hours) (Andre, 1999)

Roswell Park regimen: 500 mg/m² (bolus) on days 1, 8, 15, 22, 29, and 36 (1 hour after leucovorin) every 8 weeks (in combination with leucovorin) for 4 cycles (Haller, 2005)

See additional protocols for Gastric, Pancreatic, Anal, Bladder, Cervical, Esophageal, Head and neck, squamous cell and Hepatobilliary Cancers...

Dosage adjustment for toxicity: According to the manufacturer, treatment should be discontinued for the following:Stomatitis or esophagopharyngitis, leukopenia (WBC <3500/mm³), rapidly falling white blood cell count, intractable vomiting, diarrhea, frequent bowel movements, watery stools, gastrointestinal ulcer or bleeding, thrombocytopenia (platelets <100,000/mm³), hemorrhage

Monitoring Parameters

CBC with differential and platelet count, renal function tests, liver function tests, signs of palmar-plantar erythrodysesthesia syndrome, stomatitis, diarrhea, hemorrhage, or gastrointestinal ulcers or bleeding

Pregnancy Risk Factor

D; 

 The National Comprehensive Cancer Network (NCCN) breast cancer guidelines (v.3.2012) state that chemotherapy, if indicated, may be administered to pregnant women with breast cancer as part of a combination chemotherapy regimen (common regimens administered during pregnancy include doxorubicin, cyclophosphamide, and fluorouracil); chemotherapy should not be administered during the first trimester, after 35 weeks gestation, or within 3 weeks of planned delivery.

Drug interactions: LINK: http://www.drugs.com/drug-interactions/fluorouracil.html

A total of 252 drugs (1839 brand and generic names) are known to interact with fluorouracil.

• 49 major drug interactions (1256 brand and generic names)
• 200 moderate drug interactions (574 brand and generic names)
• 3 minor drug interactions (9 brand and generic names)

Show all medications in the database that may interact with fluorouracil.

fluorouracil ↔ multivitamins with minerals

Major Drug Interaction

Products containing folic acid may increase the effects of fluorouracil. You may be more likely to develop serious side effects such as anemia, bleeding problems, infections, and nerve damage when these medications are used together. Contact your doctor if you experience severe nausea and vomiting, diarrhea, paleness of skin, fatigue, dizziness, fainting, unusual bleeding or bruising, blood in the stools, fever, chills, body aches, flu-like symptoms, skin reactions, mouth ulcers or sores, and/or numbness, burning or tingling in your hands and feet. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Vitamin K Antagonists (eg, warfarin): Fluorouracil (Systemic) may increase the serum concentration of Vitamin K Antagonists. Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates. Consider therapy modification

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

5FluroUracil Cancer...

Zolpidem

Today's med: Zolpidem (zole PI dem) (brand name: Ambien, Edluar, Intermezzo, Zolpimist)

Drug Class: gamma-Aminobutyric Acid-ergic Agonist (Hypnotic, Miscellaneous)

Other Drugs in this class: Baclofen,Zolpidem tartrate 

Indications: Ambien®, Edluar™, Zolpimist®: Short-term treatment of insomnia (with difficulty of sleep onset); Ambien CR®: Treatment of insomnia (with difficulty of sleep onset and/or sleep maintenance)

Intermezzo®: "As needed" treatment of middle-of-the-night insomnia with ≥4 hours of sleep time remaining.

Sublinox™ (Canadian availability; not available in U.S.): Short-term treatment of insomnia (with difficulty of 

sleep onset, frequent awakenings, and/or early awakenings)

Contraindications: Hypersensitivity to zolpidem or any component of the formulation.  Canadian labeling: Additional contraindications (not in U.S. labeling): Significant obstructive sleep apnea syndrome and acute and/or severe impairment of respiratory function; myasthenia gravis; severe hepatic impairment; personal or family history of sleepwalking

Adverse Effects: >10%: Central nervous system: Headache (3% to 19%), somnolence (6% to 15%), dizziness (1% to 12%); 1% to 10%: Cardiovascular: Blood pressure increased, chest discomfort/pain, palpitation; Central nervous system: Abnormal dreams, anxiety, apathy, amnesia, ataxia, attention disturbance, body temperature increased, burning sensation, confusion, depersonalization, depression, disinhibition, disorientation, drowsiness, drugged feeling, euphoria, fatigue, fever, hallucinations, hypoesthesia, insomnia, lethargy, lightheadedness, memory disorder, mood swings, sleep disorder, stress; Dermatologic: Rash, urticaria, wrinkling; Endocrine & metabolic: Menorrhagia; Gastrointestinal: Abdominal discomfort, abdominal pain, abdominal tenderness, appetite disorder, constipation, diarrhea, dyspepsia, flatulence, gastroenteritis, gastroesophageal reflux, hiccup, nausea, vomiting, xerostomia; Genitourinary: Urinary tract infection, vulvovaginal dryness; Neuromuscular & skeletal: Arthralgia, back pain, balance disorder, involuntary muscle contractions, myalgia, neck pain, paresthesia, psychomotor retardation, tremor, weakness; Ocular: Asthenopia, blurred vision, depth perception altered, diplopia, red eye, visual disturbance; Otic: Labyrinthitis, tinnitus, vertigo; Renal: Dysuria, Respiratory: Pharyngitis, sinusitis, throat irritation, upper respiratory tract infection, Miscellaneous: Allergy, binge eating, flu-like syndrome

<1% (Limited to important or life-threatening): Agitation, anaphylaxis, anemia, angioedema, cerebrovascular disorder, cognition decreased, complex sleep-related behavior (sleep-driving, cooking or eating food, making phone calls), concentrating difficulty, cystitis, diaphoresis, dysphagia, dyspnea, edema, emotional lability, falling, hepatic function abnormalities, hyperglycemia, hyper-/hypotension, illusion, leukopenia, lymphadenopathy, migraine, orthostatic hypotension, paresthesia of the tongue (sublingual tablets), pruritus, renal failure (acute), scleritis, somnambulism (sleepwalking), speech disorder, stupor, sublingual erythema (sublingual tablets), syncope, tachycardia, thrombosis, urinary incontinence, vaginitis

**NOTE: Zolpidem is known to inhibit REM sleep.

Standard Dosing:  Oral: Adults: Note: The lowest effective dose should be used; higher doses may be more likely to impair next morning activities.Immediate release tablet, spray: 5 mg (females) or 5-10 mg (males) immediately before bedtime; maximum dose: 10 mg daily

Extended release tablet: 6.25 mg (females) or 6.25-12.5 mg (males) immediately before bedtime

Sublingual tablet:

Edluar™: 5 mg (females) or 5-10 mg (males) immediately before bedtime; maximum dose: 10 mg daily

Sublinox™ (Canadian availability; not available in U.S.): 10 mg immediately before bedtime; maximum dose: 10 mg daily

Intermezzo®: Note: Take only if ≥4 hours left before waking

Females: 1.75 mg once per night as needed (maximum: 1.75 mg/night)

Males: 3.5 mg once per night as needed (maximum: 3.5 mg/night)

Dosage adjustment with concomitant CNS depressants: Females and males: 1.75 mg once per night as needed; dose adjustment of concomitant CNS depressant(s) may be necessary.

Ingest immediately before bedtime due to rapid onset of action. Regardless of dosage form, do not administer with or immediately after a meal. 

Ambien CR® tablets should be swallowed whole; do not divide, crush, or chew. Edluar™, Intermezzo®, or Sublinox™ (Canadian availability; not available in U.S.) sublingual tablets should be placed under the tongue and allowed to disintegrate; do not swallow or administer with water.  Zolpimist® oral spray should be sprayed directly into the mouth over the tongue. Prior to initial use, pump should be primed by spraying 5 times. If pump is not used for at least 14 days, re-prime pump with 1 spray.

Drug interactions: Link: http://www.drugs.com/drug-interactions/zolpidem.html

A total of 691 drugs (3835 brand and generic names) are known to interact with zolpidem.

• 7 major drug interactions (28 brand and generic names)
• 644 moderate drug interactions (3669 brand and generic names)
• 40 minor drug interactions (138 brand and generic names)

Show all medications in the database that may interact with zolpidem.

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

ZZZZZZZZZZZZolpidem!! (get your Z's)