BLACK BOX WARNINGS ⚠️ : 1. Pioglitazone & rosiglitazone Worsen CHF & fluid retention . 2. METHADONE : respiratory depression 😰 . 3. Cigarette smoking 🚬 with ORAL CONTRACEPTIVES :- Risk of heart attack and stroke and after 35 years age more prone to get blood clots and thrombus so stroke and heart attacks are more common . 4 . MEDROXYPROGESTRONE : decreases bone density 🦴 mainly to premenopausal . 5 . Long acting beta 2 agonists : - asthma related toxicity & must combines with corticosteroids