FDA Approved Labeling Flashcards
Drug Labeling
FDA approved Labeling
- Affixed to the container or “Package insert”
- Strictly regulated by FDA
- Important component of the evaluation and approval for NDA and ANDA
- Changes in the label post NDA must be approved by FDA
FDA Current Package Insert Requirements
- Simplify the format of the package insert and make them more user friendly
- Intent is to improve patient safety and drug efficacy
- The highlights of prescribing information is to provide the most important facts for immediate access and info about benefit and risk
Off label
- Can legally prescribe and dispense for off label uses
- Manufacturers are strictly prohibited by FDA to promote products for off label uses but in 2015 a small drug company won a case in that regard
Pain Syndromes
Somatic Pain
- Localized: trauma, surgical
Visceral Pain
- Deeper pain: Cancer, Kidney stones
Neuropathic Pain
- Injury to nerves
- Seconday to disease state
- Diabetic neuropath, post herpetic pain
Psychosomatic Pain
- Mind/Body/Stress
Nociceptive Pain
- Pain that signals tissue damage through pain pathway
Non-Narcotic Analgesics: Profen, Fenac
- NSAIDs are most widely used OTC analgesics
- Salicylates: precursor to the NSAIDs (Willow Bark)
Chemical: - Profen and Fenac is selective of chemical class of SOME NSAID (they are chemically heterogenous)
Pharmacological: - COX Inhibition: MOA applicable to all NSAIDs
- Inhibitation of COX enzyme and prostaglandin is associated with inflammation & pain
Therapeutic: - Analgesic: Pain relief
- Antipyretic: Fever reducer (all have it)
- Anti inflammatory: Vary in degree depending on potency
Aspirin (Acetylsalicylic Acid, ASA)
- Not considered as NSAID because it is a precursor
- Unlike NSAIDs, it irreversibly inhibit platelet function for 7-10 days of the half
- Effective for most types of Mild-Moderate pain
- Mostly used for platelet inhabitation at a lose dose of 81mg for cardio protective effect
- Side effects: GI bleeding and tinnitus
Drug-Drug interaction: Warfarin (anticoagulant) and NSAIDs (including ASA): Increase INR (blood is thiner) and risk of bleeding
NSAIDs
Non Selective inhibitors of COX
- Inhibit both polymorphic forms of COX enzymes: COX-1 & COX-2
Partially Selective Inhibitors of COX
- Less likely to inhibit platelet aggregation to cause GI bleeding than ASA and non selective
Selective Inhibitors of COX
- Most selective of NSAID class inhibit only COX-2
- Only one drug remaining: CeleCOXIB
Non-Selective Inhibitors of COX
- IbuPROFEN (Advil)
- Naproxen (Naprosyn-Rx only; Alive-OTC)
- DicloFENAC
- NepaFENAC (Ilevroo)
- BromFENAC (Prolensa)
- Ketorolac (Toradol)
- Inddomethacin (indocin)
Non-Selective Inhibitors of COX II
Ibuprofen: Max daily adult dose is 3.2g/day
- Duexis (combination product): protect from GI effects
- There is Intravenous Ibuprofen (Caldolor)
Naproxen: Twice daily dosing
- Longer duration of action and lowest risk of cardiovascular side effects
- Used for inflammation and arthritic pain commonly
Diclofenac: Immediate/ Delayed release formulation
- Zorvolex: low dose form 18 or 35mg
- Dyloject: diclofenac sodium intravenous - discontinued
- Flector: Diclogenac epolamine 1.3% topical
Nepafenac ophthalmic suspension 0.3%: cataract surgery
Bromfenac opthalmic solution 0.07%: Cataract/ophthalmic surgery
Non-Selective Inhibitors of COX III
Ketorolac Tromethamine (Toradol): 10mg tablets
- Short tern use (not>5 days); relieve of moderate-sever pain
- Parenteral administration of NSAIDs does not eliminate possibility of GI bleeding or ulcer formation
- IV Ketorolac is great of post operative pain
Indomethacin (indocin): 25 & 50 mg capsule; SR 75mg
Combination:
Excedrin Migraine: ASA + Acetaminophen + Caffeine
Advil Dual Action: ASA + Acetaminophen
- Synergist effect for relief
Vicoprofen: Hydrocodone + Ibuprofen
- Prescription products (NSAIDS with narcotic analgesics)
Partially Selective inhibitors of COX
Erodolac:
- 300-500mf immediate release tablet
Meloxican (Mobic):
- 7.5 or 15 mg tablet
Selective Inhibition of COX-2 Classifications (COXIB)
Chemical: Diaryl-Substituted Pyrazoles
Pharmacologic: Inhibit COX-2 (NOT COX-1 isoform)
- COX-1: protect & maintain the normal lining of the stomach and intestine, protecting the stomach from the digestive juices
- COX-2: Inflammation and pain
COXIBs differ from other NSAIDs
- Substitution for patient with GI side effects from NSAIDs
CeleCOXIB (Celebrex): Analgesic + Anti-inflammatory effect=> Decreased anti-pyretic effect (50, 100, 200, 400mg capsules)
Warning: Caution in patients with risk of stroke or heart attack (no significant CV dangers) - Open heart surgery
Indications: Osteo- and rheumatoid arthritis, Primary dysmenorrhea, Familial Adenomatous Polyposis
Selective Inhibition of COX-2 Classifications (COXIB)
Celecoxib + tramadol (Segletis-2021)
- 56-44 mg
- Selective NSAID and analgesic for opioid for acute pain
Celecoxib + amlodipine (Consensi - 2018)
- 2.5mg-10mg/200 mg
- Blood pressure and selective NSAID for hypertension and osteoarthritis
Adverse Drug Reaction of NSAIDs
Coagulation Disorders:
- Increased risk of internal bleeding (caused by inhibition of platelets aggregation)
Pregnancy:
- Increased risk of miscarriage
- Avoid during 3rd trimester (ibuprofen not indicated)
- Discontinue 6-8 weeks prior to delivery
Reye’s Syndrome
- Released to aspirin and children
SJS and TEN:
- SJS: Steven Johnson Syndrome
- TEN: Toxic Epidermal Necrolysis
- Idiopathic breakdown of skin resulting in blister
- TEN > SJS in severity
Caution in certain population
Acetaminophen (Tylenol)
- Effective analgesic and antipyretic but no anti-inflammatory effects
- Not an NSAID
- No cardioprotective effects
- Does NOT increase risk of stroke or heart attack
- No GI toxicity (no bleeding)
