Migraine and headache:

Indications for: CAMBIA

Acute treatment of migraine with or without aura.

Limitations of Use:

Not indicated for prophylactic therapy. Safety and efficacy not established for cluster headache.

Clinical Trials:

  • The approval was based on data from 2 randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) that evaluated the efficacy and safety of Cambia for the acute treatment of migraine headache in adults 18 years of age and older. Patients were randomly assigned to receive 1 dose of Cambia or placebo to treat a migraine of moderate to severe pain.

  • Study endpoint included “sustained pain free”, defined as a reduction in headache severity from moderate to severe pain to no pain at 2 hours post-dose without a return of mild, moderate, or severe pain, and no use of rescue medication for 24 hours post-dose.

  • In Study 1, a greater proportion of patients treated with Cambia achieved the following pain free results compared with patients treated with placebo, respectively:

    • 2-Hour Pain Free: 24% vs 13%

    • 2–24h Sustained Pain Free: 22% vs 10%

    • 2-Hour Pain Relief: 48% vs 27%

  • In Study 2, a greater proportion of patients treated with Cambia achieved the following pain free results compared with patients treated with placebo, respectively:

    • 2-Hour Pain Free: 25% vs 10%

    • 2–24h Sustained Pain Free: 19% vs 7%

    • 2-Hour Pain Relief: 65% vs 41%

Adult Dosage:

Use lowest effective dose for the shortest duration. ≥18yrs: Take on an empty stomach; mix 1 packet (50mg) with 30–60mL of water only and drink immediately. Not interchangeable with other forms of diclofenac.

Children Dosage:

<18yrs: not recommended.

CAMBIA Contraindications:

Aspirin allergy. Coronary artery bypass graft surgery.

Boxed Warning:

Risk of serious cardiovascular and gastrointestinal events.

CAMBIA Warnings/Precautions:

Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Hypertension; monitor BP closely. Hepatic or renal impairment. Discontinue if signs/symptoms of liver disease develop, or if abnormal LFTs persist or worsen. Dehydration. Hypovolemia. Advanced renal disease: not recommended. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, and renal function in long-term therapy. Pre-existing asthma. Medication overuse headache; may need detoxification. May mask signs of infection or fever. Discontinue at 1st sign of rash or any other hypersensitivity. Elderly. Debilitated. Labor & delivery. Pregnancy (Cat.C: <30 weeks gestation; Cat.D: ≥30 weeks gestation; avoid). Nursing mothers: not recommended.

CAMBIA Classification:

NSAID (benzeneacetic acid deriv.).

CAMBIA Interactions:

Avoid concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazides), ACE inhibitors, ARBs, or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Caution with other hepatotoxic drugs (eg, acetaminophen, certain antibiotics, antiepileptics). May be affected by CYP2C9 inhibitors.

Adverse Reactions:

Nausea, dizziness; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, hypertension, anaphylactic reactions, serious skin reactions (eg, SJS, TEN), anemia.

Metabolism:

  • The formation of 4’- hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion.

  • Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3’-hydroxy- diclofenac.

Drug Elimination:

  • Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites.

  • Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.

  • The terminal half-life of unchanged diclofenac is approximately 2 hours.

Generic Drug Availability:

NO

How Supplied:

Packets—1, 9