Respiratory Depression: Respiratory depression is the most dangerous acute reaction produced
by opioid agonist preparations, although it is rarely severe with usual doses. Opioids decrease the
respiratory tidal volume, minute ventilation, and sensitivity to carbon dioxide. Respiratory
depression occurs most frequently in elderly or debilitated patients, usually after large initial doses
in non-tolerant patients, or when opioids are given in conjunction with other agents that depress
respiration. This combination product should be used with caution in patients with significant chronic
obstructive pulmonary disease or cor pulmonale and in patients with a substantially decreased
respiratory reserve, hypoxia, hypercapnia, or respiratory depression.

Hypertensive Effect: Dihydrocodeine, like all opioid analgesics, may cause hypotension in patients
whose ability to maintain blood pressure has been compromised by a depleted blood volume or who
received concurrent therapy with drugs such as phenothiazine or other agents which compromise
vasomotor tone. This product may produce orthostatic hypotension in ambulatory patients. This
combination product should be administered with caution to patients with circulatory shock since
vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Dependence: Dihydrocodeine can produce drug dependence of the codeine type and has the potential
of being abused. This product should be prescribed and administered with the appropriate degree of caution
(See Drug Abuse and Dependence section).

PRECAUTIONS
General: This combination product should be used with caution in elderly or debiliated
patients or those with any of the following conditions: adrenocortical insufficiency (e.g.,
Addison's disease); asthma; central nervous system depression or coma; chronic obstructive
pulmonary disease; decreased respiratory reserve (including emphysema, severe obesity,
cor pulmonale, or kyphoscoliosis); delirium tremens; diabetes, head injury; hypotension;
hypertension; increased intracranial pressure; myxedema or hypothyroidism; prostatic
hypertrophy or urethral structure; and toxic psychosis. The benefits and risks of opioids in
patients taking monoamine oxidase inhibitors and in those with a history of drug abuse should
be carefully considered. This combination product may aggravate convulsions in patients with
convulsive disorders, and like all opioids, may induce or aggravate seizures in some clinical settings.

Drug Interactions:
General: Sympathomimetic amines may reduce the antihypertensive effects of methyldopa,
mecamylamine, reserpine, and veratrum alkaloids.

Other CNS Depressants: Patients receiving other opioid analgesics, sedatives or hypnotics,
muscle relaxants, general anesthetics, centrally acting anti-emetics, phenothiazines or other
tranquilizers, or alcohol concomitantly with this product may exhibit additive depressant
effects on the central nervous system. When such combination therapy is contemplated,
the dose of one or both agents should be reduced. Concomitant use of dihydrocodeine with
a