MIDOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIDOL (MIDOL).
Midol is a combination product containing acetaminophen (analgesic/antipyretic via COX inhibition in CNS), caffeine (adenosine receptor antagonist), and pyrilamine (H1 antihistamine). The primary mechanism for dysmenorrhea is prostaglandin synthesis inhibition by acetaminophen.
| Metabolism | Acetaminophen is primarily metabolized in the liver via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3); minor oxidation by CYP2E1, CYP3A4, and CYP1A2 to toxic NAPQI. Caffeine is metabolized by CYP1A2. Pyrilamine is metabolized by hepatic enzymes. |
| Excretion | Renal: >90% as acetaminophen glucuronide and sulfate conjugates; unchanged drug <5%. Biliary/fecal: <5%. |
| Half-life | Acetaminophen: 2-3 hours in adults; prolonged to 4-6 hours in neonates or hepatic impairment. Caffeine: 3-6 hours; prolonged in pregnancy or liver disease. |
| Protein binding | Acetaminophen: 10-25% bound to albumin; caffeine: 25-36% bound to albumin. |
| Volume of Distribution | Acetaminophen: 0.9 L/kg; caffeine: 0.6 L/kg. Both primarily distribute into total body water. |
| Bioavailability | Oral acetaminophen: 85-98% (first-pass metabolism ~10-15%). Caffeine: ~100% orally. |
| Onset of Action | Oral: 30-60 minutes; peak analgesic effect at 1-2 hours. |
| Duration of Action | Analgesic: 4-6 hours. Antipyretic: 4-6 hours. Caffeine component may extend alertness effects but not analgesia. |
| Action Class | Opioids |
| Brand Substitutes | Bestodol 100 Injection, Tricare Injection, Tramot 100mg Injection, Supridol 100mg Injection, Tramazac Injection |
Acetaminophen 500 mg, PAM Bromide 15 mg, Pyrilamine Maleate 15 mg: 2 tablets orally every 4-6 hours as needed for dysmenorrhea; maximum 10 tablets per day.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to acetaminophen accumulation; avoid if GFR <10 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: maximum acetaminophen 2000 mg/day; Child-Pugh C: contraindicated due to acetaminophen hepatotoxicity. |
| Pediatric use | Not recommended for children under 12 years; for ages 12-17: same adult dose (2 tablets) but limit to 5 tablets per day. |
| Geriatric use | No specific adjustment; monitor for anticholinergic effects (dry mouth, confusion) from pyrilamine and PAM bromide; use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIDOL (MIDOL).
| Breastfeeding | Acetaminophen: excreted in breast milk in small amounts (M/P ratio ~0.91); considered compatible. Caffeine: excreted (M/P ratio ~0.5-0.7); levels in milk peak 1-2 hours after dose; limit to <300 mg/day to avoid infant irritability. Pyrilamine: no data; likely excreted in small amounts. Overall, short-term use at recommended doses is likely safe. |
| Teratogenic Risk | Midol typically contains acetaminophen (pregnancy category B), caffeine (category C), and pyrilamine (category B). Acetaminophen: no known teratogenicity; risk of maternal hepatotoxicity at high doses. Caffeine: low teratogenic risk at moderate doses (<200 mg/day); higher doses associated with increased risk of miscarriage and low birth weight. Pyrilamine: no known teratogenic effects. First trimester: limited data, avoid high caffeine. Second/third trimester: use cautiously; acetaminophen safe; caffeine limit <200 mg/day. |
■ FDA Black Box Warning
No FDA black box warning exists for Midol as a combination product. However, acetaminophen component carries a risk of severe liver injury in overdose.
| Serious Effects |
["Hypersensitivity to any component","Severe liver disease or active liver disease","Concurrent use of MAO inhibitors (pyrilamine component)","Pregnancy (third trimester due to antiprostaglandin effects of acetaminophen? Not established; caution)"]
| Precautions | ["Hepatotoxicity risk with acetaminophen (max daily dose 4000 mg; avoid alcohol)","Caffeine may cause nervousness, insomnia, or tachycardia","Pyrilamine may cause drowsiness; avoid driving or operating machinery","Do not use with other acetaminophen-containing products"] |
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| Fetal Monitoring | Monitor maternal liver enzymes if high-dose acetaminophen used. Monitor fetal growth if prolonged high-caffeine intake. Avoid use in severe preeclampsia or uncontrolled hypertension. |
| Fertility Effects | Acetaminophen: no known effect on fertility. Caffeine: high intake (>300 mg/day) may reduce female fertility and increase time to pregnancy. Pyrilamine: no known effect. |