Acetaminophen may cause severe hepatotoxicity in acute overdose; limit acetaminophen to <4 g/day; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Use with caution in patients with alcoholic liver disease; consuming 
3 alcoholic drinks/day may increase the risk of liver damage. Use caution in patients with known G6PD deficiency. Caffeine may cause CNS and cardiovascular stimulation as well as GI irritation in high doses. Dihydrocodeine should be used with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone), respiratory diseases including asthma, emphysema, COPD, or severe hepatic or renal insufficiency. Use caution with MAO inhibitors. This combination should be used with caution in elderly or debilitated patients, hypotension, adrenocortical insufficiency, thyroid disorders, prostatic hyperplasia, urethral stricture, seizure disorder, CNS depression, head injury or increased intracranial pressure. Causes sedation; caution must be used in performing tasks which require alertness (eg, operating machinery or driving). Safety and efficacy in pediatric patients have not been established.
Frequency not defined. Most common reactions with this combination include: Central nervous system: Dizziness, drowsiness, lightheadedness, sedation
Dermatologic: Pruritus, skin reactions
Gastrointestinal: Constipation, nausea, vomiting
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C8/9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Caffeine: Substrate of CYP1A2 (major), 2C8/9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Dihydrocodeine: Substrate of CYP2D6 (major)
Acetaminophen: See individual monograph for associated interactions.
Caffeine:
CYP1A2 inhibitors: May increase the levels/effects of caffeine. Example inhibitors include amiodarone, fluvoxamine, ketoconazole, and rofecoxib.
CYP3A4 substrates: Caffeine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, ergot derivatives, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine.
Quinolone antibiotics (specifically ciprofloxacin, norfloxacin, ofloxacin): Quinolones may increase the level/effects of caffeine.
Dihydrocodeine:
CYP2D6 inhibitors: May decrease the effects of dihydrocodeine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.
Quinidine: Quinidine may decrease the effects of dihydrocodeine.
Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced toxicity. Ethanol may also increase CNS depression.
Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
Caffeine is a CNS stimulant; use with acetaminophen and dihydrocodeine increases the level of analgesia provided by each agent.
Dihydrocodeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.
Oral: Adults: Relief of pain: Panlor® DC: 2 capsules every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 10 capsules/24 hours)
Panlor® SS: 1 tablet every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 5 tablets/24 hours)
Capsule (Panlor® DC): Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Tablet (Panlor® SS): Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg
