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Indian Frankincense (Boswellia)

  • Class: analgesic and anti-inflammatory agent.
  • Mechanism of action: boswellic acids, especially AKBA, inhibit 5-lipoxygenase and reduce leukotriene synthesis and inhibit leukocyte elastase, which are the likely mechanisms for its anti-inflammatory and analgesic properties.29
  • Use: osteoarthritis, rheumatoid arthritis.
  • Dosing: (5-Loxin) 100-250 mg daily for 90 days has been used.30
  • Adverse effects: diarrhea, nausea, abdominal pain, heartburn, itching, skin rash, headache, edema.31
  • Contraindications: hypersensitivity to Boswellia or any of its components.
  • Drug interactions:

° CYPIA2, 2C19, 2C9, 2D6, and 3A4 substrates: Boswellia inhibits cytochrome P450 enzymes, increasing drug levels of these substrates.32

=> Immunosuppressants: Boswellia has immunostimulant properties that may decrease the effectiveness of immunosuppressive drugs.33

Cautions: insufficient reliable information available about safety during pregnancy and lactation, so avoid use.

Limbrel (Flavocoxid)

  • Class: analgesic and anti-inflammatory medical food.
  • Mechanism of action: Limbrel decreases COX-2 and lipoxygenase.
  • Use: osteoarthritis.
  • Dosing: 250-500 mg BID34 (with or without food).
  • Adverse effects: jaundice, pruritus, abdominal pain, fever, rash.

° More severe adverse reactions include increases in AST and ALT, which were found to resolve completely within 3 months of discontinuation. Liver damage can occur with Limbrel, and caution should be taken.

° Primus announced a voluntary product recall on January 26, 2018, due to sustained pressure from the FDA.

  • Contraindications: patients with liver dysfunction at baseline.34
  • Drug interactions: none know n.
  • Cautions: report any signs of liver toxicity such as jaundice, fatigue, or abdominal pain.34


  • Class: analgesic and anti-inflammatory agent.
  • Mechanism of action: turmeric has anti-inflammatory properties that affect the production of cyclooxygenase-2, prostaglandins, and leukotrienes.35
  • Use: osteoarthritis, rheumatoid arthritis.
  • Dosing:

° Osteoarthritis: 500 mg twice daily for 6 weeks.36

° Rheumatoid arthritis:

  • - 250-500 mg twice daily for 8 weeks to 3 months.
  • - 400 mg three times daily for 2 weeks.
  • - 400-600 mg up to three times/day for inflammation relief (Arthritis Foundation).
  • Adverse effects: constipation, dyspepsia, diarrhea, distention, GERD, nausea, vomiting.37
  • Drug interactions:

° Anticoagulant/antiplatelet drugs: turmeric has antiplatelet effects and may increase the INR.38

° Antidiabetic drugs: turmeric and its constituent curcumin can reduce levels of blood glucose and HbAlC and potentiate the effects of antidiabetic drugs leading to an increased risk of hypoglycemia.39

=> Camptothecin: curcumin inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71%.40

° Cyclophosphamide: in an animal model, curcumin 25 g/kg appears to inhibit cyclophosphamide-induced tumor regression.40

° CYP P450 1A1, 1A2, 3A4 substrates: turmeric and its constituent curcumin inhibit some cytochrome P450 enzymes and can increase drug levels of substrates metabolized by these enzymes.41

=> Docetaxel/paclitaxel: turmeric’s constituent curcumin can enhance the bioavailability of docetaxel and increase the blood levels. Monitor concurrent use.42

° Doxorubicin: curcumin has been shown to inhibit doxorubicin-induced apoptosis of breast cancer cells by up to 65% 40

=> Estrogen: curcumin may displace the binding of estrogen to its receptors 43

=> Glyburide: pharmacokinetic research shows that curcumin 475 mg for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 DM.44

° Mechlorethamine: curcumin may inhibit mechlorethamine-induced apoptosis of breast cancer cells by up to 70% 40

° Norfloxacin: curcumin can increase blood levels of orally administered norfloxacin, increasing the effects and adverse effects of the medication.45

=> P-glycoprotein: curcuminoids and other constituents in turmeric can inhibit P-glycoprotein expression and activity, causing an increase in absorption of p-glycoprotein substrates.46

° Sulfasalazine: curcumin can cause an increase in blood levels of sulfasalazine by 3.2- fold and increase the effects and adverse effects of sulfasalazine.47

=> Tacrolimus: turmeric and its constituent curcumin inhibit CYP3A4. Avoid large doses of turmeric with tacrolimus.48

Cautions: use with caution in patients with gallstones or gallbladder disease, and patients with iron deficiency due to a risk of reduced iron absorption with turmeric administration.

Willow Bark

  • Class: analgesic and anti-inflammatory agent.
  • Use: osteoarthritis.
  • Dosing: salicin 120-240 mg daily for 2-6 weeks 49
  • Adverse effects: gastrointestinal adverse effects, itching, rash.50
  • Contraindications: allergy to aspirin since willow bark contains salicylates, allergy to salicylates.

Drug interactions:

о Acetazolamide: willow bark contains salicin and can lead to an increase in plasma levels of acetazolamide.51

=> Anticoagulant/antiplatelet: concomitant use of willow bark and anticoagulant/anti- platelet drugs can increase the risk of bleeding due to decreased platelet aggregation. Willow bark has less severe antiplatelet effects compared to warfarin.52

=> Salicylate-containing drugs: willow bark contains salicin, a plant salicylate. Willow bark may have an additive effect with other salicylate-containing drugs.53

Cautions: willow bark contains salicylates which are excreted in breast milk and have been linked to adverse effects in breast-fed infants.51

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