The best drug for widespread hives is an antihistamine. It may not cure the hives, but it will reduce their number and relieve itching. Benadryl or its generic equivalent is available without a prescription. It comes in both liquid and tablet form. Benadryl may cause drowsiness, so do not drive while taking it. Continue taking your antihistamine for a day or 2 until you are sure the hives are completely gone. Your medical provider can prescribe a non-sedating antihistamine if necessary.